ENDOKRIN

Anatomi dan Fisiologi

Dr. drh. Sri Wigati, M.Agr.Sc.

BIOSINTESIS HORMON TIROID
BIOSINTESIS HORMON
STEROID
HORMON PEPTIDA PADA SEL TARGET
MEKANISME

KERJA

HORMON

TIROID

PADA

SEL TARGET
MEKANISME

KERJA

HORMON

STEROID

PADA

SEL TARGET
CONTOH KERJA HORMON PEPTIDA
POSISI GLANDULA PITUITARY
GLANDULA PITUITARY
HORMON ANTERIOR PITUITARY
HORMON POSTERIOR PITUITARY
HUBUNGAN ANTARA HIPOTALAMUS
DENGAN ANTERIOR PITUITARY
HUBUNGAN ANTARA HIPOTALAMUS
DENGAN POSTERIOR PITUITARY
HUBUNGAN HIPOTALAMUS –
PITUITARY - GONAD
GLANDULA PARATIROID
 HORMON
PARATIROID
MEKANISME KONTROL SINTESIS VIT. D

Sinar matahari Paratiroid

U
S
7-Dehydrocholesterol PTH
U
Kulit S
Vitamin D3
Ginjal T
U Ca2+
25-OH-D3 L +
Vitamin D3 A PO4-3
N
G
25-OH-D3 1,25-(OH)2D3
Hati Ginjal
 DEFISIENSI INSULIN

Penyerapan Glycogenolisis & Lipolisis

gula oleh sel Gluconeogenesis

Gula darah Gula dalam Asam lemak

sel darah

Keton darah
Filtrasi ginjal untk gula dan
keton

H+ darah
Osmotic diuresis (acidosis)

Excresi natrium
dan air

Tekanan darah

Suplai darah ke otak Fungsi/kerja otak

 ENDOKRINOLOGI REPRODUKSI

 SISTEM ENDOKRIN PADA WANITA

 SISTEM ENDOKRIN PADA PRIA
 SISTEM ENDOKRIN TERSEBUT TERKAIT DENGAN SISTEM
REPRODUKSI BAIK PADA WANITA MAUPUN PRIA
 PUBERTAS
 HUMAN REPRODUCTION
 Human reproduction is any form of sexual reproduction resulting
in human fertilization, typically involving sexual intercourse
between a man and a woman.
 During sexual intercourse, the interaction between the male and
female reproductive systems results in fertilization of the
woman's ovum by the man's sperm.
 These are specialized reproductive cells called gametes, created
in a process called meiosis.
 While normal cells contains 46 chromosomes, 23 pairs, gamete
cells only contain 23 chromosomes,
 It is when these two cells merge into one zygote cell that
genetic recombination occurs and the new zygote contains 23
chromosomes from each parent, giving them 23 pairs.
 After a gestation period, typically for nine months, is followed by
childbirth.
 The fertilization of the ovum may be achieved by
artificial insemination methods, which do not involve sexual
intercourse.
 SEX DETERMINATION
 Chromosome characteristics determine the genetic sex of a
fetus at conception.
 This is specifically based on the 23rd pair of chromosomes
that is inherited.
 Since the mother's egg contains an X chromosome and the
father's sperm contains either an X or Y chromosome, it is the
male who determines the fetus's sex.
 If the fetus inherits the X chromosome from the father, the
fetus will be a female. In this case, testosterone is not made
and the Wolffian duct will degrade thus, the Müllerian duct will
develop into female sex organs.
 The clitoris is the remnants of the Wolffian duct.
 On the other hand, if the fetus inherits the Y chromosome from
the father, the fetus will be a male.
 The presence of testosterone will stimulate the Wolffian duct
which will bring about the development of the male sex
organs and the Müllerian duct will degrade.[2]
 FEMALE REPRODUCTIVE SYSTEM
 The female reproductive system (or female genital system)
contains two main parts: the uterus, which hosts the
developing fetus, produces vaginal and uterine secretions,
and can pass sperm through to the Fallopian tubes;
 and the ovaries, which produce the female's egg cells. These
parts are internal; the vagina meets the external organs at
the vulva, which includes the labia, clitoris and
urinary meatus. The vagina is attached to the uterus through
the cervix, while the uterus is attached to the ovaries via the
Fallopian tubes. At certain intervals, the ovaries release an
ovum, which passes through the Fallopian tube into the
uterus. If, in this transit, it meets with sperm, a single sperm
can enter and merge with the egg, fertilizing it.
Corresponding equivalent among males is the
male reproductive system.
 OVARY
 The ova are larger than sperm and have formed by the time a female is
born. Approximately every month, a process of oogenesis matures one
ovum to be sent down the Fallopian tube attached to its ovary in
anticipation of fertilization. If not fertilized, this egg is flushed out of
the system through menstruation.

 The ovaries are small, paired organs that are located near the lateral
walls of the pelvic cavity. These organs are responsible for the
production of the ova and the secretion of hormones. Ovaries are the
place inside the female body where ova or eggs are produced. The
process by which the ovum is released is called ovulation. The speed
of ovulation is periodic and impacts directly to the length of a
menstrual cycle.

 After ovulation, the ovum is captured by the oviduct, after traveling

down the oviduct to the uterus, occasionally being fertilized on its way
by an incoming sperm, leading to pregnancy and the eventual birth of a
new human being.
 The Fallopian tubes are often called the oviducts and they have small
hairs (cilia) to help the egg cell travel.
ANATOMI OVARIUM
 FERTILIZATION

 During the reproductive process, the egg is not a passive

recipient, but rather an active participant in the fertilization
process. It releases certain molecules that are essential to
guiding the sperm which allow the surface of the egg to
attach to the sperm's surface. The egg can then absorb the
sperm and fertilization begins.[1] The fertilization usually
occurs in the oviducts, but can happen in the uterus itself. A
zygote will then divide over enough generations of cells to
form a blastocyst, which implants itself in the wall of the
uterus, where it begins the processes of embryogenesis and
morphogenesis. When developed enough to survive outside
the womb, the cervix dilates and contractions of the uterus
propel the fetus through the birth canal, which is the vagina.
 MALE REPRODUCTIVE SYSTEM

 The male reproductive system contains two main divisions: the

testes where sperm are produced, and the penis.
 In humans, both of these organs are outside the abdominal cavity.
Having the testes outside the abdomen facilitates temperature
regulation of the sperm, which require specific temperatures to
survive about 2-3 °C less than the normal body temperature i.e. 37 °C.
 In particular, the extraperitoneal location of the testes may result in
a 2-fold reduction in the heat-induced contribution to the
spontaneous mutation rate in male germinal tissues compared to
tissues at 37 °C.[1]
 If the testicles remain too close to the body, it is likely that the
increase in temperature will harm the spermatozoa formation,
making conception more difficult.
 This is why the testes are carried in an external pouch viz. scrotum
rather than within the abdomen; they normally remain slightly cooler
than body temperature, facilitating sperm production.
Male reproductive system
 PUBERTY

 Puberty is the process of physical changes through which a

child's body matures into an adult body capable of
sexual reproduction to enable fertilization.
 It is initiated by hormonal signals from the brain to the
gonads: the ovaries in a girl, the testes in a boy. In response
to the signals, the gonads produce hormones that stimulate
libido and the growth, function, and transformation of the
brain, bones, muscle, blood, skin, hair, breasts, and
sex organs.
 Physical growth—height and weight—accelerates in the first
half of puberty and is completed when an adult body has been
developed. Until the maturation of their reproductive
capabilities, the pre-pubertal physical differences between
boys and girls are the external sex organs.
 On average, girls begin puberty at ages 10–11; boys at ages
11–12.[1][2]

 Girls usually complete puberty by ages 15–17,[2][3][4]

 while boys usually complete puberty by ages 16–17. [2][3][5]

 The major landmark of puberty for females is menarche, the

onset of menstruation, which occurs on average between
ages 12–13;[6][7][8][9] for males, it is the first ejaculation, which
occurs on average at age 13.
 NEUROHORMONAL PROCESS
 The endocrine reproductive system consists of the hypothalamus, the
pituitary, the gonads, and the adrenal glands, with input and
regulation from many other body systems. True puberty is often
termed "central puberty" because it begins as a process of the
central nervous system. A simple description of hormonal puberty is
as follows:
 The brain's hypothalamus begins to release pulses of GnRH.
 Cells in the anterior pituitary respond by secreting LH and FSH into
the circulation.
 The ovaries or testes respond to the rising amounts of LH and FSH by
growing and beginning to produce estradiol and testosterone.
 Rising levels of estradiol and testosterone produce the body changes
of female and male puberty.
 The onset of this neurohormonal process may precede the first
visible body changes by 1–2 years.
Components of the endocrine reproductive system

 The arcuate nucleus of the hypothalamus is the driver of the

reproductive system. It has neurons which generate and release
pulses of GnRH into the portal venous system of the pituitary gland.
The arcuate nucleus is affected and controlled by neuronal input from
other areas of the brain and hormonal input from the gonads, adipose
tissue and a variety of other systems.
 The pituitary gland responds to the pulsed GnRH signals by releasing
LH and FSH into the blood of the general circulation, also in a
pulsatile pattern.
 The gonads (testes and ovaries) respond to rising levels of LH and
FSH by producing the steroid sex hormones, testosterone and
estrogen.
 The adrenal glands are a second source for steroid hormones.
Adrenal maturation, termed adrenarche, typically precedes
gonadarche in mid-childhood.
HUBUNGAN HIPOTALAMUS –
PITUITARY - GONAD
 MAJOR HORMONES
 Neurokinin B (a tachykinin peptide) and kisspeptin (a neuropeptide),
both present in the same hypothalamic neurons, are critical parts of the
control system that switches on the release of GnRH at the start of
puberty. [83]
 GnRH (gonadotropin-releasing hormone) is a peptide hormone released
from the hypothalamus which stimulates gonadotrope cells of the
anterior pituitary.
 LH (luteinizing hormone) is a larger protein hormone secreted into the
general circulation by gonadotrope cells of the anterior pituitary gland.
The main target cells of LH are the Leydig cells of testes and the
theca cells of the ovaries. LH secretion changes more dramatically with
the initiation of puberty than FSH, as LH levels increase about 25-fold
with the onset of puberty, compared with the 2.5-fold increase of FSH.
 FSH (follicle stimulating hormone) is another protein hormone secreted
into the general circulation by the gonadotrope cells of the anterior
pituitary. The main target cells of FSH are the ovarian follicles and the
Sertoli cells and spermatogenic tissue of the testes.
 Testosterone is a steroid hormone produced primarily by the
Leydig cells of the testes, and in lesser amounts by the theca cells of
the ovaries and the adrenal cortex.

 Testosterone is the primary mammalian androgen and the "original"

anabolic steroid. It acts on androgen receptors in responsive tissue
throughout the body.
 Estradiol is a steroid hormone produced by aromatization of
testosterone.
 Estradiol is the principal human estrogen and acts on
estrogen receptors throughout the body. The largest amounts of
estradiol are produced by the granulosa cells of the ovaries, but
lesser amounts are derived from testicular and adrenal testosterone.
 Adrenal androgens are steroids produced by the
zona reticulosa of the adrenal cortex in both sexes. The
major adrenal androgens are dehydroepiandrosterone,
androstenedione (which are precursors of testosterone), and
dehydroepiandrosterone sulfate which is present in large
amounts in the blood. Adrenal androgens contribute to the
androgenic events of early puberty in girls.
 IGF1 (insulin-like growth factor 1) rises substantially during
puberty in response to rising levels of growth hormone and
may be the principal mediator of the pubertal growth spurt.
 Leptin is a protein hormone produced by adipose tissue. Its
primary target organ is the hypothalamus. The leptin level
seems to provide the brain a rough indicator of adipose mass
for purposes of regulation of appetite and energy metabolism.
It also plays a permissive role in female puberty, which
usually will not proceed until an adequate body mass has
been achieved.
 ENDOCRINE PERSPECTIVES
 The endocrine reproductive system becomes functional by the
end of the first trimester of fetal life.

 The testes and ovaries become briefly inactive around the time
of birth but resume hormonal activity until several months
after birth, when incompletely understood mechanisms in the
brain begin to suppress the activity of the arcuate nucleus.
 This has been referred to as maturation of the prepubertal
"gonadostat," which becomes sensitive to negative feedback
by sex steroids.

 The period of hormonal activity until several months after

birth, followed by suppression of activity, may correspond to
the period of infant sexuality, followed by a latency stage,
which Sigmund Freud described.[8
 Gonadotropin and sex steroid levels fall to low levels (nearly
undetectable by current clinical assays) for approximately
another 8 to 10 years of childhood. Evidence is accumulating
that the reproductive system is not totally inactive during the
childhood years. Subtle increases in gonadotropin pulses
occur, and ovarian follicles surrounding germ cells (future
eggs) double in number.
 Normal puberty is initiated in the hypothalamus, with de-
inhibition of the pulse generator in the arcuate nucleus. This
inhibition of the arcuate nucleus is an ongoing active
suppression by other areas of the brain. The signal and
mechanism releasing the arcuate nucleus from inhibition
have been the subject of investigation for decades and
remain incompletely understood.
 Leptin levels rise throughout childhood and play a part in
allowing the arcuate nucleus to resume operation. If the
childhood inhibition of the arcuate nucleus is interrupted
prematurely by injury to the brain, it may resume pulsatile
gonadotropin release and puberty will begin at an early age.
 Neurons of the arcuate nucleus secrete
gonadotropin releasing hormone (GnRH) into the blood of the
pituitary portal system.
 An American physiologist, Ernst Knobil, found that the GnRH
signals from the hypothalamus induce pulsed secretion of LH
(and to a lesser degree, FSH) at roughly 1-2 hour intervals.
 The LH pulses are the consequence of pulsatile GnRH
secretion by the arcuate nucleus that, in turn, is the result of
an oscillator or signal generator in the central nervous
system ("GnRH pulse generator").[85]
 In the years preceding physical puberty, Robert M. Boyar
discovered that the gonadotropin pulses occur only during
sleep, but as puberty progresses they can be detected during
the day. [86]
 By the end of puberty, there is little day-night difference in
the amplitude and frequency of gonadotropin pulses.
 ADRENARCHE AND PUBARCHE

 Regulation of adrenarche and its relationship to maturation of the

hypothalamic-gonadal axis is not fully understood, and some
evidence suggests it is a parallel but largely independent process
coincident with or even preceding central puberty.

 Rising levels of adrenal androgens (termed adrenarche) can usually

be detected between 6 and 11 years of age, even before the
increasing gonadotropin pulses of hypothalamic puberty.

 Adrenal androgens contribute to the development of pubic hair (

pubarche), adult body odor, and other androgenic changes in both
sexes.
 The primary clinical significance of the distinction between
adrenarche and gonadarche is that pubic hair and body odor changes
by themselves do not prove that central puberty is underway for an
individual child.
 Hormonal changes in boys
 Early stages of male hypothalamic maturation seem to be very similar to
the early stages of female puberty, though occurring about 1–2 years
later.
 LH stimulates the Leydig cells of the testes to make testosterone and
blood levels begin to rise.
 For much of puberty, nighttime levels of testosterone are higher than
daytime.

 Regularity of frequency and amplitude of gonadotropin pulses seems to

be less necessary for progression of male than female puberty.

 However, a significant portion of testosterone in adolescent boys is

converted to estradiol.
 Estradiol mediates the growth spurt, bone maturation, and epiphyseal
closure in boys just as in girls.
 Estradiol also induces at least modest development of breast tissue (
gynecomastia) in a large proportion of boys. Boys who develop mild
gynecomastia or even developing swellings under nipples during puberty
are told the effects are temporary in some male teenagers due to high
levels of estradiol.
 Another hormonal change in males takes place during the
teenage years for most young men. At this point in a male's
life the testosterone levels slowly rise, and most of the
effects are mediated through the androgen receptors by way
of conversion dihydrotestosterone in target organs
(especially that of the bowels).
 Hormonal changes in girls
 As the amplitude of LH pulses increases, the theca cells of the
ovaries begin to produce testosterone and smaller amounts of
progesterone.

 Much of the testosterone moves into nearby cells called

granulosa cells.

 Smaller increases of FSH induce an increase in the aromatase

activity of these granulosa cells, which converts most of the
testosterone to estradiol for secretion into the circulation.

 The remaining testosterone, together with adrenal androgens is

responsible for the typical androgenic changes of female puberty:
pubic hair, other androgenic hair as outlined above, body odor, acne.

 The bioactivity of testosterone is to a large degree limited by SHBG

which in turn is mainly controlled by estradiol and prolactin levels
(estradiol stimulates, prolactin decreases SHBG synthesis).
 Rising levels of estradiol produce the characteristic estrogenic
body changes of female puberty: growth spurt, acceleration of
bone maturation and closure, breast growth, increased fat
composition, growth of the uterus, increased thickness of the
endometrium and the vaginal mucosa, and widening of the
lower pelvis.

 As the estradiol levels gradually rise and the other

autoamplification processes occur, a point of maturation is
reached when the feedback sensitivity of the hypothalamic
"gonadostat" becomes positive.

 This attainment of positive feedback is the hallmark of female

sexual maturity, as it allows the mid cycle LH surge necessary
for ovulation.

 Growth hormone levels rise steadily throughout puberty. IGF1

levels rise and then decline as puberty ends. Growth finishes
and adult height is attained as the estradiol levels complete
closure of the epiphyses.
 ACTIVIN AND INHIBIN
FUNCTIONS

 Activin and inhibin are two closely related protein complexes

that have almost directly opposite biological effects.

 Identified in 1986,[1][2] activin enhances FSH biosynthesis and

secretion, and participates in the regulation of the
menstrual cycle.
 Many other functions have been found to be exerted by activin,
including roles in cell proliferation, differentiation, apoptosis,[3]
metabolism, homeostasis, immune response, wound repair,[4]
and endocrine function.

 Conversely inhibin downregulates FSH synthesis and inhibits

FSH secretion.[5]
 The existence of inhibin was hypothesized as early as 1916;
however, it was not demonstrated to exist until
Neena Schwartz and Cornelia Channing's work in the mid
1970s, after which both proteins were molecularly
characterized ten years later. [6]

STRUCTURE
 Activin is a dimer composed of two identical or very similar
beta subunits.

 Inhibin is also a dimer wherein the first component is a beta

subunit similar or identical to the beta subunit in activin.
However, in contrast to activin, the second component of the
inhibin dimer is a more distantly-related alpha subunit.[7][8]

 Activin, inhibin and a number of other structurally related

proteins such as anti-Müllerian hormone,
bone morphogenetic protein, and growth differentiation factor
belong to the TGF-β protein superfamily. [9]
 SECRETION SITES OF ACTIVIN
 Activin is produced in the gonads, pituitary gland, placenta, and other
organs:
 In the ovarian follicle, activin increases FSH binding and FSH-induced
aromatization. It participates in androgen synthesis enhancing LH action in
the ovary and testis. In the male, activin enhances spermatogenesis.
 Activin is strongly expressed in wounded skin, and overexpression of
activin in epidermis of transgenic mice improves wound healing and
enhances scar formation. Its action in wound repair and skin
morphogenesis is through stimulation of keratinocytes and stromal cells in
a dose-dependent manner. [14]
 Activin also regulates the morphogenesis of branching organs such as the
prostate, lung, and especially kidney. Activin A increased the expression
level of type-I collagen suggesting that activin A acts as a potent activator
of fibroblasts.
 Lack of activin during development results in neural developmental
defects.
 On February 3, 2015, the University of Virginia School of Medicine
announced results that indicate activin A plays a role in lung cancer
metastasis, and possibly metastases of other forms of cancer. [15]
 SECRETION SITES OF INHIBIN
 In both females and males, inhibin inhibits FSH production. Inhibin does
not inhibit the secretion of GnRH from the hypothalamus.[16][17] However, the
overall mechanism differs between the sexes:
 In females
Inhibin is produced in the gonads, pituitary gland, placenta, corpus luteum
and other organs.
FSH stimulates the secretion of inhibin from the granulosa cells of the
ovarian follicles in the ovaries. In turn, inhibin suppresses FSH.
Inhibin B reaches a peak in the early- to mid-follicular phase, and a second
peak at ovulation.
Inhibin A reaches its peak in the mid-luteal phase.
Inhibin secretion is diminished by GnRH, and enhanced by
insulin-like growth factor-1 (IGF-1).

 In males
It is secreted from the Sertoli cells,[18] located in the seminiferous tubules
inside the testes. Androgens stimulate inhibin production; this protein may
also help to locally regulate spermatogenesis.[citation needed]
 Mechanism of action
 Activin
 As with other members of the superfamily, activins interact with two
types of cell surface transmembrane receptors (Types I and II) which
have intrinsic serine/threonine kinase activities in their cytoplasmic
domains:
 Activin type 1 receptors: ACVR1, ACVR1B, ACVR1C
 Activin type 2 receptors: ACVR2A, ACVR2B
 Activin binds to the Type II receptor and initiates a cascade reaction
that leads to the recruitment, phosphorylation, and activation of Type
I activin receptor. This then interacts with and then phosphorylates
SMAD2 and SMAD3, two of the cytoplasmic SMAD proteins.
 Smad3 then translocates to the nucleus and interacts with SMAD4
through multimerization, resulting in their modulation as
transcription factor complexes responsible for the expression of a
large variety of genes.
 Inhibin
 In contrast to activin, much less is known about the mechanism of
action of inhibin, but may involve competing with activin for binding
to activin receptors and/or binding to inhibin-specific receptors. [8]
 Clinical significance
 Quantification of inhibin A is part of the prenatal quad screen that
can be administered during pregnancy at a gestational age of 16–18
weeks. An elevated inhibin A (along with an increased beta-hCG,
decreased AFP, and a decreased estriol) is suggestive of the
presence of a fetus with Down syndrome.[19] As a screening test,
abnormal quad screen test results need to be followed up with more
definitive tests.
 It also has been used as a marker for ovarian cancer.[20][21]
 Inhibin B may be used as a marker of spermatogenesis function and
male infertility.
 The mean serum inhibin B level is significantly higher among fertile
men (approximately 140 pg/mL) than in infertile men (approximately
80 pg/mL).[22] In men with azoospermia, a positive test for inhibin B
slightly raises the chances for successfully achieving pregnancy
through testicular sperm extraction (TESE), although the association
is not very substantial, having a sensitivity of 0.65 (95% confidence
interval [CI]: 0.56–0.74) and a specificity of 0.83 (CI: 0.64–0.93) for
prediction the presence of sperm in the testes in non-obstructive
azoospermia.[23]
 A mutation in the gene for the activin receptor ACVR1 results
in fibrodysplasia ossificans progressiva, a fatal disease that
causes muscle and soft tissue to gradually be replaced by
bone tissue.[24]
 This condition is characterized by the formation of an extra
skeleton that produces immobilization and eventually death by
suffocation.[24]
 The mutation in ACVR1 causes activin A, which normally acts
as an antagonist of the receptor and blocks osteogenesis
(bone growth), to behave as an agonist of the receptor and to
induce hyperactive bone growth.[24] On 2 September 2015,
Regeneron announced that they had developed an antibody for
activin A that effectively cures the disease in an animal model
of the condition.[25]
 Mutations in the ACVR1 gene have also been linked to cancer,
especially diffuse intrinsic pontine glioma (DIPG).[26][27][28]
 See also