Fisiología del crecimiento

Jorge Sanhueza S. PhD

■ Concepto de crecimiento.
■ Parámetros: talla, peso, perímetros y perímetro craneal.
■ Procesos: Hipertrofia, hiperplasia, diferenciación, morfogénesis
■ Evaluación: osificación (edad ósea), desarrollo sexual.
■ El crecimiento como parámetro general de “salud”.
 Etapas del crecimiento

• Desarrollo ontogénico.
• Prenatal. Factores condicionantes:
• Alimentación materna
• Estado de la placenta (fumadoras)
• Presión intrauterina (partos gemelares)
• Sexo del conceptus
• Edad madre
• Orden de nacimiento
• Factores genéticos-étnicos.
• Factores geográficos (altitud)
• Hormonas: efectos de la diabetes y del
hipotiroidismo maternos.
 Etapas del crecimiento
• Postnatal Factores:
• Genéticos: poligénico
• Ambientales: alimentación, enfermedades, ejercicio, afecto, clima.
• Talla RN: 50 cm en X.
• Peso: 2,5-3,5 kg en X.
• Escasa maduración cerebral en el momento del nacimiento.
• Velocidad de crecimiento: “a saltos”
• 1er año: 25 cm
• 2º año: 12,5
• 3er año y siguientes hasta pubertad: 6,25.
• Falta de correlación entre talla al nacer y adulto.
• Diferencias intersexos : aumento de la velocidad en pubertad. Curvas de
crecimiento. Percetiles.
 Regulación Endocrina del crecimiento:

• Somatotropina (GH)- Factores análogos a la insulina (IGFs)

• Hormonas Tiroideas.

• Insulina.

• Esteroides sexuales.

• Coticoesteroides.
Hormona del crecimiento

944 NORMAL AND ABERRANT GROWTH

10
5
Ser Arg Leu Phe Asp Asn Ala Met
1 Ile Pro Leu Leu Arg
Pro
Thr
15 Ala
His 20
Phe Arg
H2N Leu
95 100 His
Gln
90
Leu Arg Ser Val Phe Ala Asn Ser Leu
Gln Phe Leu
Val Tyr 105
Val Ala
Glu Pro Gly
Ala 25
85 Trp
Leu
Ser
Phe
Ser Asn Asp
Gln Ser
Ile Asp Thr
Leu 140 Val 110
Leu 135 Tyr
80 Leu 145 Tyr
Thr Gln Lys Phe Ile Gln Gly
Ser Tyr Thr Asp Gln
Ser Lys Arg
Phe Pro 30
Ile Leu Glu
Asp Ser
Arg Gly Leu Phe
Thr
Leu
Asn 180 Asp 130 Lys 115 Glu
75 Leu
150 Ser
Ile Arg Leu
Glu Asp Glu
Val
Gln Ser Gln Phe
Leu
His 185 Val Arg CyS
Thr 175 Leu Ala
Leu Glu
Asn Glu Glu Arg Tyr 35
Asn Gly Ser CyS Glu
Gly Val Gly Ile
Ser Asp Phe Gly
COOH 125 120 Pro
70 Lys Asp 190 Lys Met Ile
Gln
Ala
155 Leu Thr Gln
Lys
Asp Glu
Gln
Thr
Leu
160 170 Met Gln 40
Glu
Leu
Lys Asn 165 Asp Lys
Glu Tyr Gly Leu Lys Tyr
Arg Leu Tyr CyS Phe Arg
Asn Ser
Ser
65 Pro
Thr Leu
Phe
Pro Ile Asn Gln
Ser Glu Ser Phe CyS Leu Ser Thr Gln Pro
60 45
55 50
Figure 24-15 Covalent structure of human growth hormone. (From Chawla RK, Parks JS, Rudman D. Structural variants of human growth hormone: biochemical,
genetic and clinical aspects. Annu Rev Med. 1983;34:519-547.)

PRL, chorionic somatomammotropin (CS, placental lacto- effects on the regulation of GH synthesis. The pulsatile
gen), and a 22-kd GH variant (GH-V) that is secreted only secretion of GH in vivo is believed to result from a simul-
by the placenta and differs from pituitary GH by 13 amino taneous reduction in hypothalamic somatostatin release
acids.72 The genes encoding these proteins most likely and increased GHRH release.90 Conversely, a trough of GH
evolved from a common ancestral gene, despite being secretion occurs when somatostatin is released in the face
located on different chromosomes (chromosome 6 for PRL of diminished GHRH activity.
and chromosome 17 for GH).73 The genes for GH, PRL, and Regulation of the reciprocal secretion of GHRH and
placental lactogen share a common structural organiza- somatostatin is imperfectly understood. The hypothalamus
tion, with four introns separating five exons. The GH sub- integrates signals for stress, sleep, hemorrhage, fasting,
family contains five members, with genes located on a hypoglycemia, and exercise through the secretion of mul-
78-kilobase (kb) section of chromosome 17; the 5′ to 3′ tiple neurotransmitters and neuropeptides to regulate the
order of the genes is GH, a CS pseudogene, CS-A, GH-V, release of these hypothalamic factors and ultimately to
and CS-B.74 Normally, about 75% of GH produced by the influence GH secretion. This physiologic phenomenon
pituitary is of the mature, 22-kd form. Alternative splicing forms the basis for a number of GH-stimulatory tests
Hormona del crecimiento
 Regulación de la secreción
de GH :GHIH y SST

• Secreción pulsatil (6-11 pulsos/día).

• Vida media 6-20 min.

• GHIH y SST: Somatostatina, otros neuropétidos y

hormonas
 Acciones GH
• Efectos: crecimiento, anabolizante, lipolítica, diabetogénica,
lactotrópica.

• Órganos diana: hígado, músculo, hueso.

• Síntesis de somatomedinas (IGF1,IGF2)

• GH en envejecimiento.
 Somatomedinas (IGFs)
• IGF1: Vida media larga debido a BP. Síntesis : aumento progresivo
durante la infancia (aumento final en pubertad). Dependencia de
estado nutritivo.
• IGF2: Síntesis constante a lo largo de la vida, alta importancia
durante la gestación.

• Efectos IGFI:
• Insulínicos: hipoglucemiante, Disminución AGL.
• Mitógenico, diferenciación.
• Acción regulada con GH en el crecimiento longitudinal del hueso
GH e IGF’s
 Prolac'na
PRH

Hormona liberadora de prolactina (PRH)

Prolactina Prolactina

La secreción de esta hormona esta

influenciada por una hormona liberadora de
prolactina proveniente del hipotálamo. Su
control es realizado por la hormona liberadora
de prolactina (PIH), que probablemente es el
neurotransmisor dopamina.
 Prolac'na
M: 10 a 25 pg/L
H: 10 a 20 pg/L

Deriva de un precursor común con GH.

Secreción pulsaBl (REMmax) 30 pg/L.

Semivida 50 min.

D2, glucocor'coides y T3: reguladores.

TRH, VIP: es'muladores.

Otros que elevan: ejercicio, comidas, relaciones

sexuales, cirugías menores, anestesia general, infarto
agudo de miocardio y otras formas de estrés agudo.
Unas 10 veces durante el embarazo y disminuyen
rápidamente en las dos semanas siguientes al parto.
 Funciones
• Proliferativas y secretoras.

• Desarrollo y funcionalidad del

tejido mamario.

• Funciones adaptativas durante

la gestación.

• Disminuye la líbido.

• Inhibe las aromatasas.

• Supresión de GnRH y
gonadotrofinas hipofisiarias.

• Inhibe la maduración de los

folículos.
Hiperprolac'nemia
>100 pg/L
 Hiperprolac'nemia
>100 pg/L
Los prolac'nomas son los adenomas hipofisiarios
más comunes (30%).

Los prolac'nomas 'enden a calcificarse de forma

muy frecuente.

No confundir con hiperprolac'nemia secundaria a

fármacos (haloperidol, reserpina, feno'azinas,
etc.) o por exceso de estrogenos, TRH o falla
renal.
 Eje Hipotálamo-Hipófisis-Gonada

de GnRH Kispeptina (+)

Neuroquinina B (+)
Glutamato (+)
estudio del cerebro de
Noradrenalina (+)
pusieron que las neuronas Leptina (+)
olfatoria y luego migran al ON (+)
cuentran distribuidas
reóptica y áreas más caudales
asal Neuropeptido Y (-)
CRH (-)
Dinorfina (-)
La GnRH se une a un receptor específico GABA (-)
Estradiol (-)
a la interacción de señales de orientación, Su activación altera la conformación de una
adhesión, factores de crecimiento y proteína G acoplada

neurotransmisores
Se activa el sistema adenilciclasa y
proteinquinasa C

halamo-pituitary-gonadal axis. T.M. Plant. J Endocrinol. 2015 August ; 226(2): T41 T54. doi:10.1530/JOE-15-0113.
Permite el ingreso de calcio a la célula
(canales transmembrana) y activación de la
proteinquinasa C
1056 PUBERTY: ONTOGENY, NEUROENDOCRINOLOGY, PHYSIOLOGY, AND DISORDERS

Prenatal growth restriction

Obesity, visceral fat

1056

Prenatal growth restriction

Obesity, visceral fat

Pubertad
The Developed World
PUBERTY: ONTOGENY, NEUROENDOCRINOLOGY, PHYSIOLOGY, AND DISORDERS

The average age of menarche in industrialized

countries
the past
The Developed World

150
hasagedecreased
The average
years, and
by 2 to
of menarche in industrialized

Unitedin the
countries has decreased by 2 to 3 months per decade over
the past 150 years, and in the States,
3 months per de
European
United States, the
the decrease
has been the pastapproximately 2 this
tosecular
has been approximately 2 to 3 months per decade during
century (Fig. 25-4). 12,16
However, 3 months
trend per decad
has slowed in developed countries such 12,16
the past century (Fig.Europe 25-4). However, this secu
Insulin resistance and as the United
compensatory hyperinsulinemia
States, Australia, and Western since approximately
Insulin resistance and has slowed better health, in developed countries such as th
1940, presumably due to improved socioeconomic status,
and the benefits of urbanization. There is a
compensatory hyperinsulinemia Adrenals:
Androgens
Liver:
SHBG
Ovary:
Androgens
States,developed
Fat cells:
Aromatase
Australia, world, where andlower Western
relatively small range of ages of menarche in the well-off
socioeconomic classesEurope do since appro
1940, Chronic presumably due totheimproved
not have an increased burden of disease or malnutrition.
diseases previously increased age of menarche, socioeconom
Bioavailability of sex steroids
better and health,
tions (e.g., celiac and the benefits
delay in menarche is still associated with serious condi-
disease, asthma) of urbanization. T
that are not adequately

relatively small
decreased,range
suggesting aof agesnumber
treated. The standard deviation of the mean age of men-
arche also diminished of menarche
of in th
Adrenals: Liver: Ovary: Fat cells: ?
developed world, Teasingwhere lower
those maturing very late, as might be found among disad-
vantaged people. 17
out the various socioeconomic c
factors involved
Androgens SHBG Androgensadrenarche, Aromatase
Promotes earlier Triggers earlier
pubarche
and/or thelarche
central precocious
puberty not have further an
in any
increased
remaining,
long-term study and burden
more subtle secular trends will
newer methodologic of disease or maln
require

approaches in areas where nutrition and health are optimal

Figure 25-3 Proposed endocrine pathways linking childhood obesity Chronicand diseases
or close 18 previously
to it. Remarkably, increased
a reverse secular trend is the age of m
reported in certain areas of Europe, leading to a later age
andgrowth delay in menarche is still associated with serio
insulin resistance to early pubertal onset and maturation. Childhood obesity
and the predisposition to visceral adiposity after intrauterine of menarche. This has been attributed to a resurgence of
restraint lead to insulin resistance and peripheral hyperinsulinemia. Insulin physical and psychological stress, as was seen in previous
acts on various organs, including the adrenals, liver, ovary, and fat
Bioavailability of sex steroids tions
cells, to
increase sex steroid bioavailability. Elevated circulating and tissue sex steroid
(e.g., celiac
eras (e.g., World War II).disease, asthma) that are not ad
18

There are cross-sectional and limited longitudinal data

treated.
levels in obese prepubertal children can have only mild local effects or
activate early hypothalamic-pituitary puberty and early reproductive matura- fromThethe 20thstandard
century demonstratingdeviation
a secular trendof
19
in the mean age
the United States, including ethnic influences. The age of
arche menarche
tion. (From Ahmed ML, Ong KK, Dunger DB. Childhood obesity and the timing
of puberty. Trends Endocrinol Metab. 2009;20:237-242.) also decreased,
in the United States was suggesting
12.8 years accordinga to diminished n
? those Health
the 1973 U.S. National Center for Health Statistics National
maturing Education Study,very 20
late,
and data asThird
from the mightNational be found amo
Health and Nutrition 17 Examination Survey (NHANES III,
Promotes earlier Triggers earlier vantaged people.
1988-1994) indicate that theTeasing
median age at out the
that time wasvarious factors
enhance survival in difficult intrauterine circumstances set
adrenarche, pubarche central
the stageprecocious
for later disorders. Insulin resistance, which
be the basis for most of these complications or may be just
inmayany 17remaining, more subtle Sweden
secular trends wi
and/or thelarche onepuberty
feature of the syndrome, may spare nutrients from
in muscle, leaving them available for the brain. This mech-
further
use long-term studyNorwayand newer meth
anism can minimize central nervous system (CNS) approaches in areas where nutrition and health ar
Finland
damage Denmark
in the fetus during periods of malnutrition. 16
18
Figure 25-3 Proposed endocrine pathways linking childhood obesity and or close to it. Remarkably, Holland
a reverse secular

Age at menarche (years)

United Kingdom
insulin resistance to early pubertal onset and maturation.
DETERMINANTS Childhood OF THE obesity AGE OF reported 15 in certain areas ofU.S.A. Europe, leading to a
and the predisposition to visceral adiposity after PUBERTY intrauterine
AND MENARCHE growth of menarche. This has been attributed to a resu
restraint lead to insulin resistance and peripheral hyperinsulinemia.
Although historical records showInsulin that puberty occurs physical
at an
14
14 and psychological stress, as was seen in
earlier age today, most evidence derives from reports of the
acts on various organs, including the adrenals, liver, ovary, (Table
age of menarche and 25-1).fat cells, to is removed
Age of menarche eras (e.g., World War II). 18
increase sex steroid bioavailability. Elevated circulating and tissue sex steroid
by several years from the first sign of secondary develop-
ment in girls, 12,13
and modern studies demonstrate correla- There13 are13cross-sectional and limited longitud
levels in obese prepubertal children can have age only
tion mild local effects or
coefficients of only 0.37 between age
of onset of puberty, suggesting both unique andfrom
of menarche and

activate early hypothalamic-pituitary puberty and factors

earlyexertingreproductive
effects on these matura- 14
ages. Changes in health
similar the 20th century demonstrating a secular
19
the col-United States, including ethnic influences. T
12 1950 1960 1970
and socioeconomic status in regions where data were
tion. (From Ahmed ML, Ong KK, Dunger DB. Childhood obesity and the timing
lected during different decades leads to complexity in the
interpretation of modern national data.
of puberty. Trends Endocrinol Metab. 2009;20:237-242.) Recalled age of menarche is considered to be accurate
menarche in the United 1840 1860 1880 1900 1920
States was 12.8 years acc
Year of Menarche
1940 1960 1980

within 1 year (in 90% of cases) up to 30 years after the

event. Contemporaneous recordings are performed with
the 1973 Figure U.S. National
25-4 The changes Center
in age at menarche between 1840for Health Statistics
and 1978
illustrate the advance in the age at menarche in Western Europe and the
agriculture, and the growth of cities and later urban centers,
menarche occurred later, and the complexity of life led to FETAL ORIGINS
a delay in the attainment of an adult role in society. In

Pubertad
modern times, the age of menarche has decreased, but the There are long-lasting ef
age of social adulthood still occurs later, causing a discrep- neonatal growth. As seen
ancy that probably has not occurred previously in human weight followed by rap
history. catch-up growth) leads t
pubertal development. P
for-gestational-age (SGA
of menarche7 and the ag
20 effect of increased post
overweight or obesity, al
25-3 describes the relati
Menarche tissue and early puberty.
that a lower expected
Mismatch observed infant’s birth
Age (years)

appropriate for materna

10 sex, and gestational age
(BMI) at 8 years led to
Psychosocial who are longer and ligh
maturation Industrial Social greater BMI values at 8
revolution complexity
and social and nutritional arche.10 Rapid weight ga
Agriculture
settlement improvement overload but not thereafter correl
and with earlier menarc
Many international s
0 low birth weight or catc
20,000 2000 200 Present in adulthood. Birth weig
years years years not prematurity alone—
ago ago ago cular mortality and p
Figure 25-2 The relationship between the likely range of ages of menarche
syndrome (i.e., metaboli
(green) and achievement of psychosocial maturity (pink) from 20,000 years consists of hypertension
ago to the current day. The mismatch in timing between these two processes elevated triglyceride lev
is a novel phenomenon. (From Gluckman PD, Hanson MA. Evolution, develop- features. This outcome
ment, and timing of puberty. Trends Endocrinol Metab. 2006;17:7-12.) metabolic programming,
ment. Values do not increase in Klinefelter’s syndrome, in are about 1500 to 2000 transducer GnRH neurosecre-
which the initial rise levels off during midpuberty.310 INSL3 tory neurons, which are not segregated into a specific
may serve as another indication of Leydig cell function. nucleus but are functionally interconnected. These

Pubertad
GnRH neurons comprise the GnRH pulse generator,
Prostate-Specific Antigen. Prostate-specific antigen (PSA) which drives and controls the pituitary gonadal com-
is detectable in male and female cord blood and in the ponents, stimulates the release of LH and FSH, and
serum of infants, but PSA concentrations decrease to unde- translates neural signals into a periodic, oscillatory
tectable levels during childhood. PSA concentrations rise
to the measurable range with the onset of puberty in the
male and correlate with the progressionPUBERTY: ONTOGENY,
of pubertal NEUROENDOCRINOLOGY, PHYSIOLOGY, AND DISORDERS
stage, 1083
the size of the testes, serum LH and testosterone concentra- TABLE 25-10
311,312
tions,Hypothalamus
and, presumably,GnRH the size of the prostate.
GRF SRIF PSA The highHypothesis
rate of boneofturnover
the Control
in earlyof the Onset
puberty followed
values are increased to the + pubertal range
+ in boys
− with
by a decrease in periosteal
of Human apposition and endosteal resorp-
Puberty
idiopathic CPP, and they decrease with GnRH agonist tion within cortical bone and decreased bone remodeling
treatment.
Pituitary LH, FSH ? GH within cortical
1. Centraland cancellous
Dogma: The CNS bone mediated
exercises by major
the only apoptosis
restraint on the
+ of chondrocytes in the growth plate and osteoclasts within
onset of puberty. The neuroendocrine control of puberty is mediated
+ + cortical andby cancellous bone,GnRH-secreting
the hypothalamic is mediated in part by estro-
neurosecretory neurons in the
gen. This leads
medialtobasal
a reduction
hypothalamus, in bone
whichturnover
act as an markers
endogenous at pulse
Circulation Estrogens + IGF I menarche,generator
reflecting the closure of the epiphyseal growth
CENTRAL NERVOUS SYSTEM 266
(oscillator).
plates. 2. The development of reproductive function is a continuum extending
AND PUBERTY + + Endocrine
Girls withfromTurner
sexual syndrome
differentiation without
and the estrogen
ontogeny exposure
of the hypothalamic-
retain elevated markers of bone turnover. Prepubertal
pituitary-gonadal system in the fetus to the attainment girlsof full sexual
Two independent but associated processes (controlled by with Turner syndrome
maturation and tend to lose bone, but that ceases
fertility.
Growth plate when estrogen therapy begins; administration of estrogen
different mechanisms but closely linked temporally)
Autocrine are 3. In the prepubertal child the GnRH
may best be started earlier in these patients.267 During
pulse generator, operative in the
Bone in the increased secretion
involved + ofParacrine
sex steroids in the fetus and infant, functions at a low level of activity (the juvenile pause)
puberty and into the third decade, estrogen has an ana-
peripubertal and pubertal IGF period.
I In the first process, ad- because of steroid-independent and steroid-dependent inhibitory
bolic effect on the osteoblast and an apoptotic effect on
mechanisms.
renarche, the increase in adrenal androgen secretion284,313 the osteoclast, increasing bone mineral acquisition in the
Figure 25-18 Interactions of the major growth-promoting hormones
precedes by approximately 2 years the second process, axial and4. appendicular
Puberty represents the reactivation
skeletons. (disinhibition)
Evolutionary theoryofsug-
the CNS
during puberty. Plus (+) indicates stimulatory action; minus (−) indicates
gonadarche, which is a consequence of the pubertal gests that suppressed
reac-
GnRH pulse
positive effects generator on
of estrogen characteristic of late infancy and
bone density,
inhibitory action. Circulating insulin-like growth factor 1 (IGF1) arises mainly
added to childhood,
mechanical leading to increased
loading, amplitude
allow women andtofrequency
carry of GnRH
tivation of the hypothalamic-pituitary gonadotropin-
from liver, but other tissues also contribute (i.e., endocrine action). Growth pulsatile for
discharges, to increased stimulation of process
the pituitary
hormone (GH) and gonadal steroids
314,315 have a direct stimulatory effect on the increased weight pregnancy and lactation; this
gonadal apparatus. gonadotropes,
is unnecessary after and finally to gonadal
reproduction, andmaturation. Hormonally, puberty
osteoporosis
generation of IGF1 (i.e., paracrine action) locally in bone and cartilage cells.
The
For onset ofthepuberty
simplification, is afor
feedback loops consequence
IGF1 and gonadal of maturational
steroids on the becomes more is initiated
commonby theatrecrudescence
menopause.of augmented pulsatile GnRH and
268

changes,
hypothalamic including
pituitary unittheare development of secondary
omitted. FSH, follicle-stimulating hormone;sexual Testosteronegonadotropin
may also secretion,
have mainly
a directat night.
action on bone in
characteristics, the adolescent
GRF, growth hormone–releasing growth
factor; LH, spurt,
luteinizing hormone;theSRIF,
attain-the human male, because androgen receptors are found in
CNS, central nervous system; GnRH, luteinizing hormone–releasing hormone.
somatotropin release–inhibiting factor.
ment of fertility, and psychosocial changes, all emanating human tibial growth plates in osteoblasts and chondro-
From Grumbach MM, Kaplan SL. The neuroendocrinology of human puberty:
cytes, osteocytes, mononuclear cells, and endothelial cells
from the disinhibition or reaugmentation of the hypotha-
of bloodanvessels
ontogenetic
in the perspective.
bone marrow. In Grumbach
269 MM, Sizonenko
Androgens that PC, Aubert ML,
lamic GnRH pulse generator and gonadotropin secretion, cannot be eds. Control of to
aromatized theestrogen
Onset of still
Puberty.
cause Baltimore, MD: in
an increase Williams & Wilkins,
causing
with a an increase
mutation in thein ERα gonadal
gene (ESR1)steroid secretion
or the CYP19A1(Table 1990:1-68.
growth rate, © 1990, the
presumably dueWilliams & Wilkins Co.,
to interaction withBaltimore.
these
gene encoding aromatase continue to grow, lack a pubertal receptors. The greater increase in periosteal bone deposi-
growth spurt, and have open epiphyses and osteope- tion, the resultant thickening of cortical bone and greater
150,151,255-257
nia. Estrogen treatment of men with aromatase bone strength, and the greater bone dimensions269 in boys

and a striking increase in bone mass.

http://bookmedico.blogspot.com
deficiency leads to epiphyseal closure, cessation of growth,
260-262
Patients with
probably result from direct effects of testosterone. Andro-
gens may protect men against osteoporosis by maintenance
 582 PHYSIOLOGY AND PATHOLOGY OF THE FEMALE REPRODUCTIVE AXIS

Follicular phase Ovulation Luteal phase

Ovary

Proliferative phase Secretory phase

Endometrium

Menses

LH P
Serum hormone levels

E2 InhA P
LH
InhA
InhB E2 E2
InhB LH
LH
E2
P P P
FSH FSH LH FSH
LH LH FSH
E2 E2 LH
InhB
InhA InhA LH
FSH FSH
InhB

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
A Days

Hypothalamus
 Granulosa Theca

Mitochondrion

CYP11A1

Basement membrane
FSHR StAR
Pregnenolone

Circulation
Cholesterol
FSH Gsα ATP

Cyclase
SF-1
ATP HSD3B2
Preovulatorio
Cyclase

cAMP
CYP17A1
cAMP Gsα
Androstenedione Androstenedione
SF-1 CYP19A1
LRH-1
LHCGR LH
Follicular Estrone
fluid HSD17B1
Estradiol Cytosol
A

Granulosa Theca

LDL
Mitochondrion
Mitochondrion
Circulation

CYP11A1
CYP11A1
Cholesterol StAR StAR
LH LHCGR Pregnenolone
Pregnenolone

HSD3B2
Cholesterol
ATP
Cuerpo luteo
Cyclase

SF-1
G sα
SF-1 Progesterone HSD3B2
ATP LRH-1 cAMP
Cyclase

CYP17A1
Gsα
cAMP Androstenedione Androstenedione
CYP19A1
Gsα
LHCGR LH
Estrone
HSD17B1
FSH FSHR
Estradiol Cytosol
Cytosol
B
s necessary for fibroblast in a continuous fashion, these cell types contrib-
corpus luteum ute to circulating estradiol levels because of their relative
e level follows
Estrógenos
estradiol level,
haracterized by
us luteum con-
Adrenal Ovary
rone, estradiol,
e again toward Aromatase
w cycle. If preg-
blastocyst, the
ogesterone and
are maintained
hCG acts as a A E1,E2

s (e.g., activin,
Circulation Circulation
nd steroidogen-
duced by gran-
e action of FSH A
Skin
ptor formation A
Aromatase
id formation in Aromatase
reased produc- E1 E1,E2
17β-HSD
creased activin E1 E2
Adipose
ds in the theca 17β-HSD
tissue Circulation
ctors and cyto- E2 Physiologic Pathologic
recursor andro- Brain Breast cancer
ultimately of Breast Endometriosis
Skin
Peripheral Estrogen Blood vessel
n in theca cells tissues target tissues
granulosa cells
Figure 17-21 Estrogen biosynthesis in women.The biologically active estro-
enous IGF pro- gen, estradiol (E ), is produced in at least three major sites: (1) by direct
 Hormonas placentarias
Maternal
CAT
T4
Estradiol Cortisol
T3
T M

11β-HSD
/CO
SD

MD
MDI
β-H

MAO

I3
3
17

Placenta Estrone MET Cortisone T2 rT3

Estrone Cortisone T4
rT3
MET
T2

Fetal
Figure 22-1 Placental neutralization of biologic activity of hormones during
maternal-fetal transfer. The neutralizing enzymes, 17β-hydroxysteroid dehy-
drogenase (17β-HSD) and 11β-HSD, are shown. See text for details. CAT,
catecholamines; COMT, catechol O-methyltransferase; MAO, monoamine
oxidase; MDI3, type 3 iodothyronine monodeiodinase; MET, metanephrines;
rT3, 3,3′5′ (reverse) triiodothyronine; T2, diiodothyronine; T3, 3,5,3′ triiodo-
thyronine; T4, thyroxine.

Placental 17β-HSD is considered to prevent passage of

excessive estrogens to the fetus by catalyzing inactivation
Hormonas placentarias
Hormonas placentarias
TABLE 21-1

Hormonas
Hormones, Peptides, and Growth Factors
Produced by the Placenta
Hypothalamic Analogues and Neuropeptides
Anandamide (endocannabinoid)
Corticotropin-releasing hormone
Dopamine
Met-enkephalin

placentarias
Ghrelin
Gonadotropin-releasing hormone
Growth hormone–releasing hormone
Melatonin
Neuropeptide Y
Oxytocin
Somatostatin
Substance P
Thyrotropin-releasing hormone
Urocortin
Vasoactive intestinal peptide
Pituitary Analogues
α-Melanocyte-stimulating hormone
β-Endorphin
Chorionic corticotropin
Chorionic gonadotropin
Placental lactogen
Placental variant growth hormone
Steroid Hormones
Estrogens
Progesterone
Growth Factors and Other Hormones
Activins
Adrenomedullin
Angiotensinogen
Basic fibroblast growth factor
Calcitonin
Colony-stimulating factor
Endothelin 1
Epidermal growth factor
Erythropoietin
Follistatin
Hepatocyte growth factor
Inhibins
Insulin-like growth factor type 1
Insulin-like growth factor type 2
Interleukins
Leptin
Leukemia inhibitory factor
Metastin
Nerve growth factor
Oncomodulin
Osteopontin
Parathyroid hormone–related protein
Platelet-derived growth factor
Pro-early placental insulin-like peptide
Renin
Transforming growth factor-α and -β
Tumor necrosis factor-α
Vascular endothelial growth factor
Other
Corticotropin-releasing hormone–binding protein
Insulin-like growth factor–binding protein
Nitric oxide
Prostate-specific antigen
Hormonas placentarias
826 ENDOCRINE CHANGES IN PREGNANCY

55 progesterone.54 The decidua may influence h

50 tion through paracrine mechanisms.8 Decidual in
45 stimulates hCG secretion in cultured tro
40 whereas decidual prolactin and an 8- to 10-
hCG (IU/mL) protein inhibit hCG production.62
35
HCG may regulate its own production to s
30 The hCG receptors are present on the surface
25 blastic cells, and the addition of hCG to place
20 culture stimulates cAMP production and prom
15 eration and differentiation of the cytotroph
10 syncytiotrophoblasts.50 Both hCG mRNA and h
5 tion are stimulated by analogues of cAMP or
activate adenylate cyclase, probably through
0
kinase.50,60 The net effect of an increase in sync
0 4 8 12 16 20 24 28 32 36 40 blast mass and cAMP levels is enhanceme
secretion.
Weeks after last menstrual period
The placenta is not the only site of hCG
Figure 21-4 Mean (± standard error) levels of maternal serum human Immunoreactive hCG has been found by im
chorionic gonadotropin (hCG) throughout normal pregnancy. (From Braun- chemistry or by immunoassay of extracts of a
stein GD, Rasor J, Danzer H, et al. Serum human chorionic gonadotropin levels of normal tissues, including spermatozoa, test
throughout normal pregnancy. Am J Obstet Gynecol. 1976;126:678.) trium, kidney, liver,CHANGES
colon, gastric tissue, lu
ENDOCRINE IN PREGNANCY 829
heart, fibroblast, brain, and pituitary gland
hormone is synthesized in some fetal tissues.
of the trophoblastic mass. HCG is first detected in maternal 7 itary appears to be the major hPL source of hCG or

serum 6 to 9 days after conception.4 The levels rise in a 6 material present in nonpregnant 0.06 individuals.
logarithmic fashion, peaking 8 to 10 weeks after the last tive and bioactive hCG has been partially pu
Placental

Serum hPL (g/mL)

500 5 weight
menstrual period, followed by a decline to a nadir at 18 pituitary glands; the material is secreted in v

Pl. wt.
Placental weight (g)

hPL
400 4 0.04
weeks, with subsequent levels remaining constant until pituitary cells and has been shown by immun
3
delivery (Fig. 21-4).53 A hyperglycosylated form of hCG 300
istry to be present in gonadotroph-type cells
63,64 0.02
produced by the cytotrophoblasts is the major form of hCG
Figure 21-6 Placental weight (Pl. wt.), maternal serum
200 2 contain hLH or human FSH. hPL
during the first 2 to 3 weeks after
concentrations implantation;
of human placental lactogen (hPL), afterward,
and 100 1 Immunoreactive hCG has Pl. wt. been measured i
the ratio of hPL to Pl. wt. during pregnancy. (From Selen-
the normally glycosylatedkow HA,form
Saxena BN, produced by the
Dana CL. Measurement syncytio-
and patho- 0 normal, nonpregnant individuals, with the h
trophoblast predominates physiologicthroughout the rest of preg-
significance of human placental lactogen.
Pecile A, Finzi C, eds. The Feto-Placental Unit. Amsterdam:
In: 4 centrations
8 12 16 20 found
24 28 32 in36postmenopausal
40 women.
51,52
nancy. The placentaExcerpta
alsoMedica,
secretes
1969:340.) free subunits. During menopausal women, this material is secreted i
Weeks of gestation

the first 13 weeks of pregnancy, relatively more β-subunit fashion in parallel with hLH pulses, and during
is synthesized than α-subunit, and throughout the remain- menstrual cycle, the immunoreactive hCG sh
Lactogeno placentario
Diferenciación sexual
848 ENDOCRINOLOGY OF FETAL DEVELOPMENT

insulin-like family and is secreted by Ley

Targeted disruption of the Insl3 gene is asso
maldevelopment of the gubernaculum and b
torchidism.151 Insl3 is also secreted by theca
LHX9 postnatal ovary, and females homozygous for
DMRT1 SF1 tions are subfertile with deregulation of the e
GATA4 In human females, differentiation of ov
Gonadal
LIM1 during the 7th week of gestation, in the abs
ridge The gonadal blastema differentiates into inte
GATA4 medullary cords containing the primitive
EMX2 referred to as oogonia. The cords degenerate,
WT1 layers of surface epithelium, containing indi
Primordial Bipotential oogonia, appear. By 11 to 12 weeks of gestatio
SRY DAX1 germ cells gonad dividing oogonia are surrounded by cord cell
cortex; the medulla at this time consists largel
SOX9 Steroidogenic
SF1 DAX1 tive tissue.152 At 12 weeks of gestation, primiti
precursors
cells begin to replicate and many of the large
SOX8 the deepest layers of the cortex enter their
SOX9 division. Primordial follicles are first observed
DHH weeks of gestation, and the number increases r
WNT1 after.153 However, the number of oocytes p
declines, from a peak of 3 to 6 million at 5 m
Stertoli Theca tion to approximately 2 million at term.16,1
Testis cells cells Ovary proliferation and apoptosis are ongoing sim
Proliferating oocytes cluster, but the clusters
Leydig Follicular
cells
with the development of follicles because
cells oocytes enfolded by developing granulosa cell
dial follicles) survive.16,153 By 5 months of ge
during the 7th month, stroma-derived thecal c
around the primordial follicles as they matur
Testosterone AMH Estrogens follicles. This process continues after birth, ag
Figure 22-9 Summary of the molecular and cellular events of gonadal dif- ing toward the superficial layers. Each fetal o
ferentiation. AMH, antimüllerian hormone or müllerian inhibiting substance; about 15 mg at 14 weeks of gestation and 30
DHH, desert hedgehog. See text for details. (Molecular cascades developed at birth.152 The number of surviving primary
from Harley VR, Clarkson MJ, Argentaro A. The molecular action and regulation birth correlates with the duration of subsequen
of the testis-determining factors, SRY (sex determining region of the Y chromo- tal ovulation. Interstitial cells with chara
some) and SOX9 (SRY-related high-mobility group [HMG] Box 9). Endocr Rev. steroid-producing cells are present after 12
2003;24:466-487; and Park SY, Jameson JL. Minireview: transcriptional regulation during the third trimester theca cells with s
of gonadal development and differentiation. Endocrinology. 2005;146: capacity surround the developing follicles.1
1035-1042.)
aromatase activity also is present, but few if
weeks’ gestation in humans and may be considered com-
plete with the development of secondary sexual character-
istics and fertility (i.e., production of viable gametes) after
puberty. Sex development is a dynamic process that requires
the appropriate and timely interaction of a multitude of
genes, proteins, signaling molecules, paracrine factors,
in ovarian development usually first manifest in adoles-
cence. Ovarian development and differentiation has been
viewed in the past as a default process that occurs in the
absence of the chromosomal, genetic, and endocrine
signals deemed actively necessary to “make a male.”
Although male sex differentiation is undoubtedly a more

Diferenciación sexual
and endocrine stimuli.5-9 Marked differences in the basic
mechanisms of sex determination, differentiation, and
active developmental process—as defined in the classic
experiments of Alfred Jost12—studies of gene expression

Mesoderm

Sertoli cells Leydig cells Testosterone

10
nmol/L

Testis descent

Male external External

genital differentiation genital growth

Wolffian duct stabilization

Germ cell Müllerian duct
migration regression

4 5 6 7 8 9 10 11 12 13 14 15 40
Gestation (weeks)
Figure 23-1 Events temporally related to sex differentiation in the male fetus. Mesoderm refers to the tissue source for Sertoli and Leydig cell formation.
The continuous line depicts the rise in fetal serum testosterone, with a peak concentration of about 10 nmol/L (300 ng/dL).

http://bookmedico.blogspot.com
 23
22 Boys Height velocity 23 Girls Height velocity
21 22
20 21
19 20
18 19
17 18
16 17
15 16
14 15
13 14
cm/yr

12 13

cm/yr
11 12
10 11
9 10
8 9
7 8
6 7
5 6
4 5
3 4
2 3
97
1 2
97
3 50 1
3 50
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Age (years) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Age (years)
Figure 24-9 Height velocity chart for boys constructed from longitudinal
observations of British children. The 97th, 50th, and 3rd percentile curves Figure 24-10 Height velocity chart for girls constructed from longitudinal
define the general pattern of growth during puberty. Shaded areas indicate observations of British children. The 97th, 50th, and 3rd percentile curves
velocities in those children with peak velocities occurring up to 2 standard define the general pattern of growth during puberty. Shaded areas indicate
deviations before or after the average age depicted by the percentile lines velocities in those children with peak velocities occurring up to 2 standard
(Up arrows, diamonds, and down arrows mark, respectively, the 97th, 50th, and deviations before or after the average age depicted by the percentile lines
3rd percentiles of peak velocity when the peak occurs at these early or late (Up arrows, diamonds, and down arrows mark, respectively, the 97th, 50th, and
limits.) (Modified from charts prepared by Tanner JM and Whitehouse RH from 3rd percentiles of peak velocity when the peak occurs at these early or late
data published in references 9, 1211, and 1899. Reproduced with permission limits.) (Modified and reproduced with permission of J.M. Tanner and Castle-
of J.M. Tanner and Castlemead Publications, Ward’s Publishing Services, Herts, mead Publications, Ward’s Publishing Services, Herts, United Kingdom.)
United Kingdom.)
 gestation to maximal levels at 35 to 40 weeks. Free T4 levels
also increase as a consequence of the increase in T4 produc-
tion. The increases in plasma TSH and T4 levels during the
third trimester reflect a progressive maturation of hypotha-

Hormonas lamic pituitary control and of thyroid gland respon-

siveness to TSH. Pituitary TSH secretion is responsive to

tiroideas 200

10
Funciones:
4 rT3

T3, T3S, rT3, rT3S, T4S (nmol/L)

150
1. Median la maduración de: hígado, 8
corazón, tejidos adiposo pardo y huesos.
2. Regulación del desarrollo de la coclea. TSH

TSH (mU/L)
3

T4 (nmol/L)
6
3. Diferenciación y maduración del SNC en T4 100
periodos críticos, abundantes receptores
en cerebro, cerebelo, corteza auditiva y 2 4 rT3S
visual.
• Neurogenesis y migración neural 50
T4S
1 2
(5-24). T 3S
• Diferenciación neuronal, creciemiento T3
dendrítico y axonal, sinaptogenesis y 0 0
gliogénesis desde los 6 meses al
0 20 30 40 2 4 6
postparto).
Fetal age Postnatal age
• Mielinización y sintesis de enzimas para (wk) (wk)
neurotransmisores, desde el segundo Figure 22-8 Patterns of change of fetal plasma thyroid-stimulating hormone
trimestre hasta 24 meses postparto. (TSH), thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), and iodothyro-
nine sulfates (T4S, rT3S, and T3S) during gestation and in the neonatal period.
The patterns for T4S and rT3S are based on limited 30-week data. (Data from
references 109, 329, 330.)
 Progesterona
• Funciones en mujeres no gestantes:

1. Cambios secretores del endometrio

(fase lutea).

• Funciones en la gestación:

2. Relajación uterina.

3. Inmunotolerancia.

4. Perfusión uterina.

5. Desarrollo mamario.

6. Natriuresis.
 Estrógenos
• Funciones en mujeres no gestantes:

1. Cambios proliferativos del endometrio (fase

folicular).

• Funciones en la gestación (tercer trimestre):

1. Medición urinaria materna (viabilidad fetal).

2. Vascularización uterina.

3. Crecimiento y desarrollo de la musculatura

uterina.

4. Relajación del tono visceral materno.

5. Regulación de la contracción uterina y

relajación de ligamentos pélvicos.

6. Antivirilización de feto femenino.

 (CYP11A1 or P450scc) and C11/C18 hydroxylation of the release. Midgestation fetal plasma corticotropin concentra-
parent steroid structure (CYP11B1/CYP11B2 or P450c11/ tions average about 55 pmol/L (250 pg/mL), levels that

Cambios hormonales previo

aldosterone synthase). A fifth enzyme, expressed by the
smooth endoplasmic reticulum, exhibits both 3β-HSD and
∆4, ∆5-isomerase activities.60,61 Quantitative differences in
the relative activities of these enzymes are found between
cells derived from the fetal versus the definitive zones, and
maximally stimulate fetal adrenal steroidogenesis, and
concentrations are higher throughout gestation than in
postnatal life, although they fall near term (Fig. 22-6).16,60
Arginine vasopressin (AVP) and catecholamines also are
significant stimuli for fetal ACTH secretion.73

GHD).31,39
al parto
these differences are largely due to regulated steroidogenic
gene transcription.60
The fetal zone has relatively high steroid sulfotransfer-
ase activity, and because of the low 3β-HSD and high sul-
The paradox of human fetal adrenal function is that
steroidogenesis is programmed largely to production of
inactive products.60 The gland is maximally stimulated to

fotransferase activities, the major steroid products of the 6000

described fetal adrenal are DHEA, DHEAS, pregnenolone sulfate,
adotropic
-44 several ∆53β-hydroxysteroids, and limited amounts of ∆53-
Muta- 35ketosteroids, including cortisol and aldosterone.60,61 The
en identi- DHEAS
d without definitive zone contributes only a small fraction of total 4000
fetal adrenal steroid output. Glucocorticoids are synthe-
eodomain sized in the first trimester due to transient expression

ACTH (pmol/L) and steroids (nmol/L)

n patients 20
of type 2 3β-hydroxysteroid dehydrogenase (HSD3B2),
nsorineu- which is maximal between 8 and 9 months of gestation.67 2000
en identi- The hypothalamic-pituitary-adrenal axis is sensitive to
Plasma concentration (nmol/L)

cerebellar glucocorticoid-mediated IGF2feedback at this time; 46XX 200

d later in fetuses with steroidogenic defects (e.g., in CYP21 or CYP11)
F1 (previ- 15lack cortisol and have an elevated ACTH drive that results
e specific in excess production of fetal androgens at a time when the Cortisone
PRL, and genital and scrotal folds are sensitive to androgen expo- 150
rior pitu- sure, resulting in virilization IGF1 of female genitalia.67
GH, TSH, Cholesterol, the major substrate for fetal adrenal ste-
n keeping 10
roidogenesis, is derived from circulating low-density lipo-
n and dif- proteinhPL(LDL) and from PRL de novo adrenal synthesis. 100 Cortisol
ons in the
LDL-cholesterol, largely of fetal liver and testicular origin,
described
contributes 70% of the total. The fetal zone contains more
ncy.52 No ACTH
es of con- 5LDL bindingGH sites and manifests a greater rate of de novo
cholesterol synthesis than does the definitive zone, in 50
for other,
keeping with its greater steroidogenic activity. Both ACTH
and angiotensin II receptors (AT1 and AT2) are present on
fetal adrenal cells early in gestation. ACTH stimulates
0steroid production by activating StAR and increasing deliv- 0
ery10of substrate 10 20 30 40 2 4 6
20 cholesterol30 to P450scc;
40 2 angiotensin
4 6 II inhib-
nd secrete its 3β-HSD activity and promotes DHEA production in the Fetal age (wk) Postnatal age (wk)
Gestational age (wk) Postnatal age (wk)
H content fetal zone.60 Both fetal adrenal cortisol and placental estra- Figure 22-6 Patterns of change of fetal plasma adrenocorticotropic
o 45 nmol Figure diol
22-4 regulate
Patterns of hepatic
change of synthesis
fetal plasma human placental lactogen
of cholesterol in the fetus.
(hPL), growth hormone (GH), prolactin (PRL), insulin-like growth factor 1 is fetal hormone (ACTH), cortisol, cortisone, and dehydroepiandrosterone sulfate
GH con- The major stimulus to fetal adrenal function (DHEAS) during gestation and in the neonatal period. The trend of average
ge of 1 to (IGF1), and insulin-like growth16,60,68
factor 2 (IGF2) during gestation and in the
neonatalpituitary
period. TheACTH. Although
shaded area indicates placental
the range of fetal hCG
plasma may
hPL support values is shown for each hormone in nanomoles per liter. Notice the broken
o a mean early adrenal
concentrations. (Data from growth, the involution of the adrenal gland
references 323-325.) scale for DHEAS. (Data from references 60, 326-328.)
n. Plasma
e second
 Surfactant release Beta-adrenergic receptors
Lung water Surfactant synthesis

Cardiac output
Blood pressure
Peripheral Promote
resistance ductus closure

Glycogen
Catecholamines Glycogenolysis Cortisol
T4 to T3

Glucagon Promote islet

Insulin maturation

NE to E

Thermogenesis

BAT
Figure 22-13 Actions of cortisol and catecholamines during fetal adaptation to the extrauterine environment. The prenatal cortisol surge acts to promote
functional maturation of several organ systems. The neonatal catecholamine surge triggers or potentiates a number of the extrauterine cardiopulmonary and
metabolic functional adaptations that are critical to extrauterine survival. See text for details. BAT, brown adipose tissue; E, epinephrine; NE, norepinephrine;
T3, triiodothyronine; T4, thyroxine.
Parto
Lactancia
Control hormonal del calcio
 Control hormonal del calcio
El Calcio (Ca +2)

El calcio entra al cuerpo por absorción intestinal de calcio (Ca+2) de la dieta y se pierde
principalmente a través de la excreción urinaria.

Dentro del cuerpo el calcio se encuentra en distintos reservorios funcionales

denominados “pools”. Una variedad de hormonas actúan para regular los niveles de
Ca+2 al controlar tanto el intercambio entre estos reservorios de calcio como la tasa de
absorción y excreción del cuerpo.

El calcio es el quinto elemento por orden

de abundancia en el organismo. Se

Ca +2
encuentra principalmente en el hueso en
una concentración del 99% unido a
fosfato formando cristales de
hidroxiapatita y el 1% restante
distribuidos en el liquido intravascular,
intersticial e intracelular.

Individuo adulto 70 kgs Aprox. 1 kg de calcio

La concentración sérica de calcio es de 8.5-10.5

mg/dl
 Control hormonal del calcio
El Calcio (Ca +2)

El calcio se encuentra en un estrecho margen, evidenciando una regulación

homeostática estrecha que no permite que sus variaciones fisiológicas excedan +/-
1.5 mg/dl.

El calcio sérico total se compone de tres fracciones:

1. Ionizado (47%) Ca +2

2. Unido a proteínas (47%)(albúmina y otras globulinas)

3. En complejo con los ácidos orgánicos (6%) (fosfatos citratos y bicarbonatos.

 Control hormonal del calcio
Reservorios de Ca+2 corporal

Soluble • Citosol
0.2 mg • Núcleo

Intracelular

• Membrana plasmática
Insoluble • Retículo endoplásmico
Ca++ 9 g (0.9%) • Mitocondrias
corporal
total

Soluble Fluído
1 g (0.1%) extracelular

Extracelular

Insoluble • Huesos
1 kg (99%) • Dientes
 Virtualmente todos los procesos fisiológicos
utilizan Ca++ intra y/o extracelular

Ca++ libre intracelular citosólico

•Contracción muscular
• Segundo mensajero •Secreción hormonal
intracelular •Metabolismo glucógeno
Coordinación •Diferenciación, proliferación
• Cofactor de enzimas y división celular

Ca++ ionizado extracelular

• Coagulación sanguínea, integridad esquelética, adhesión inter-

celular y excitabilidad neuromuscular

• Primer mensajero extracelular (rol “hormone-like”) a través de su

interacción con el CaR

Brown EM. Am J Med, Febrero 1999;106:238-253

 Balance normal de calcio
Dieta
1000 mg
Absorción
500 mg 350 mg
Formación ósea Fluído
extracelular Secreción fecal
Resorción ósea endógena
500 mg 250 mg

10,000 mg 9,900 mg
Intestino
Carga filtrada Reabsorción
de calcio renal
Hueso
900 mg

Riñón

100 mg
 Control hormonal del calcio
Regulación del Ca+2 corporal

Los mecanismos de control actúan regulando dos variables principales .

La concentración de calcio libre

en el fluido extracelular Periodo corto

Contenido de calcio corporal Mediano y largo plazo

total

Asumiendo que el calcio en la dieta es el adecuado, la regulación de la

concentración de calcio depende principalmente de dos hormonas la
paratohormona y la vitamina D, con la contribución menos importante de una
tercera hormona, la calcitonina.
 Control hormonal del calcio
Regulación del Ca+2 corporal

Parathormona (PTH)
Hormona proteica producida por cuatro glándulas paratiroides localizadas posteriormente a
lo lobos de la glándula tiroides en el cuello.

Es responsable de la regulación de la concentración de Ca+2 libre en el fluido extracelular y

es esencial para la vida.

[Ca+2] plasmático. = Parathormona

Tiene cuatro acciones principales:

Estimulación de la liberación de Excreción urinaria de fosfatos

calcio en el hueso

Reabsorción de Ca+2 en los Estimulación de la tasa de

túbulos renales. conversión de la vitamina D
 Control hormonal del calcio
Regulación del Ca+2 corporal

Vitamina D
Es una vitamina liposoluble que proviene de dos fuentes principales:

La dieta vitamina D2 Pescado, hígado, leche

irradiada con luz ultra violeta
(UV)

La piel vitamina D3 (colecalciferol) La radiación UV de la luz

solar convierte un derivado del
colesterol (7-
dehidrocolesterol) en vitamina
D3 en la piel
 Control hormonal del calcio
Regulación del Ca+2 corporal

Vitamina D
Es una vitamina liposoluble que proviene de dos fuentes principales:

Pescado, hígado, leche

La dieta vitamina D2 irradiada con luz ultra violeta
(UV)
La radiación UV de la luz
La piel vitamina D3 (colecalciferol) solar convierte un derivado del
colesterol (7-
dehidrocolesterol) en vitamina
Colecalciferol D3 en la piel

Parathormona y bajas
concentraciones de fosfato
Hígado plasmático
25-hidroxicolecalciferol

Este es el metabolito más

Riñón activo y es responsable de
la mayoría de las acciones
1,25 dihidrocolecalciferol de la vitamina D
 Control hormonal del calcio
Regulación del Ca+2 corporal

Vitamina D
La vitamina D actúa elevando los niveles plasmáticos de Ca+2 mediante:

Aumento de la tasa de Estimulación de la absorción

captación intestinal de calcio intestinal de fosfato

Vitamina D

Estimulación de la reabsorción Estimulación de la resorción

de calcio y fosfato en el riñón osteoclástica del hueso

Mineralización del tejido

osteoide recientemente formado
(importante durante el
crecimiento)
 Control hormonal del calcio
Regulación del Ca+2 corporal

Calcitonina
Esta hormona se secreta en las células C de la glándula tiroides.

Reduce la tasa de liberación

Secretada en periodos de
de calcio al fluido extracelular
hipercalcemia es una
y por lo tanto reduce la
mecanismo protector a los
concentración de Ca+2
aumentos anormales.
plasmático.