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Biosintesis Hormon

Reproduksi

Hypothalamus/
Pituitary/Reproductive Organ Axis

Mekanisme Kerja Hormon


Steroid

Mekanisme
Steroid hormones penetrate the plasma
membrane and bind to intracellular
receptors in the nucleus or cytoplasm.
Hormone binding activates the
receptor, hormone response elements,
HRE on DNA to initiate transcription
and formation of the proteins that
express the hormonal response.

Reseptor Steroid
Membrane receptors that interact with kinases.
estradiol (E2) binds to an intracellular receptor
protein (ER) that dimerizes and translocates to the
nucleus
Estradiol also affects ion channels and G-proteincoupled receptors, independent of the ER nuclear
transcription factors
receptor complex, made of the receptor protein
and coactivators, binds to the palindromic
sequences (GCTAATCG) that constitute the
estrogen response element (ERE) and affect
gene transcription

Steroid

Cholesterol

Steroid
Cortex Adrenal : Steroid
Cortisol
Androgen

Laki-laki: Testosteron
Wanita : Estrogen dan progesteron

Male

Testis
Sel Leydig :androstenediol, androstenedione,
testosterone, dihydrotestosterone, dan
dehydroepiandrosterone (DHEA)
Sel Sertoli: merubah testosterone menjadi
estrogen (<); estradiol(E2)
(spermatogenesis).
FSH dan LH: proliferation Leydig cells
LH upregulates 3-hydroxysteroid
dehydrogenase, (last step in testosterone
formation)

Testis

Testis.
Testicular androgens : mostly produced
by the Leydig cells under the influence
of pituitary luteinizing hormone (LH).
Sertoli cells: sperm proliferation and
maturation and convert androgens to
estrogens via aromatase
Dihydrotestosterone via 5-reductase
secrete inhibin to regulate LH release

FSH- LH
FSH & LH: glycoprotein
hormones,synthesized and secreted by a
single class of pituitary cells
LH: Leydig cells
Receptors: heterotrimeric G-proteins (cyclic
AMP )
activates protein kinase A, promote
steroidogenesis, gene transcription, and other
cellular functions

FSH : Sertoli cells in the germinal epithelium

Actions of FSH and LH on the testis.

Regulation, hormonal products, and interactions


between Leydig and Sertoli cells

Biosintesis Testosteron &


Progesteron

Dihydrotestosterone (DHT)

Intracellular mechanism by which LH


stimulates testosterone synthesis.

Aromatase
Adipose tissue is an important source
of the enzyme aromatase that
converts androgens to estrogen.

Metabolisme testosteron

Female

Biosintesis estrogen

Biosintesis estrogen
three hydroxylation
steps, each of which
requires O2 and
NADPH.
The aromatase
enzyme complex :
P450
monooxygenase

Hormonal and ovarian events during the menstrual


cycle.

Biosintesis Female Hormone

FSH & LH
Ovari: control the menstrual cycle.
FSH : ovarian granulosa cell proliferation and
aromatase activity to allow production of E2.
E2 increases, FSH stimulates increased LH
responsiveness.
E2 and inhibin suppress FSH production at the level
of the hypothalamus and pituitary
release of a selected oocyte from th ovary (ovulation)
and transformation of granulosa cells into the
secretory luteinized cells of the corpus luteum.
Luteal cells make large amounts of P4, but also E2
and inhibin

FSH-LH
pregnancy does not occur : LH, sufficient to
support the corpus luteum (for very long).
P4, E2, and inhibin levels drop, FSH levels
rise. Menstruation begins and the cycle
repeats.
pregnancy, luteal P4 supports the pregnancy
until hormonal support is taken over by the
placenta (typically 79 weeks of gestation).
ovarian E2 and P4 directs the growth and
differentiation of the uterine endometrium
to prepare it for embryo implantation.

Prolactin & GH
Prolactin : controls the initiation of lactation. In
contrast to other pituitary hormones, it is not
negatively regulated by classic feedback loops but
rather by
local autocrine and paracrine factors
Neurotransmitters
peripherally produced steroid hormones.
Ovarian E2 and pituitary TRH are strong stimuli for prolactin
production.

Growth hormone (GH), insulin-like growth factors


(IGFs), IGF-binding proteins (IGFBPs), and IGF
receptors of the somatotropic axis enhance ovarian
steroidogenesis

Theca & granulosa cell cooperation in


estrogen synthesis

LDL, low density lipoproteins; cAMP , cyclic adenosine monophosphate.


PKA , protein kinase A; CREB , cyclic AMP response element binding
protein; StAR , steroid acute regulatory protein; P450c17 , 17
-hydroxylase/lyase; 17 HSD , 17 hydroxysteroid dehydrogenase.

Theca & granulosa..


Theca cells produce androgens in response to LH .
Granulosa cells respond to FSH mainly by
aromatizing androgens to estrogens and to
some extent by producing pregnenolone from
cholesterol
Granulosa cells : limited in their capacity to
produce pregnenolone ;
little access to circ. cholesterol delivered by LDL
express few LDL receptors
minimal levels of P450scc needed to convert cholesterol
to pregnenolone

Theca & Granulosa cells


THECA
direct capillary blood supply and express high levels of
LDL receptors, and high levels of P450scc and P450c17.
metabolize the 21 carbon pregnenolone to the 19 carbon
androstenedione, but lack aromatase, and hence cannot
synthesize estrogens.

Granulosa
express ample aromatase, but cannot produce its 19
carbon substrate because they lack P450c17.
However, granulosa cells readily aromatize androgens
provided by diffusion from the theca interna.

Eff ects of Estrogen and Progesterone on the


Reproductive Tract

Menopause
Cessation of ovarian follicular development with resultant
marked decreases in circulating estrogen, inhibin, and
P4 levels.
Ovarian androgen production remains relatively intact.
Decreased estrogen and inhibin release, consequently
FSH levels rise.
hot fl ashes, insomnia, and depressed mood that are commonly
found in periand early postmenopausal women.
Estrogen deficiency: tissue atrophy and loss of elasticity in the
breast, vagina, and skin.

estrogen antagonizes the effects of parathyroid hormone


on Ca 2+ mobilization in bone and since estrogen deficiency
increases osteoclast activity, postmenopausal women
are at increased risk for osteoporosis

Signaling of the Breast


The suckling reflex: sensory impulses that
travel from the nipple to the brain with
breast-feeding
Prolactin: aid in continued milk
production.
Prolactin inhibits
secretion of FSH directly
indirectly through inhibition of the GnRH pulse
generator and appropriate pulsatile secretion
of GnRH

OXYTOCIN
Oxytocin: uterus to contract
and causes the cervix to
stretch.
Oxytocin secreted in response
to suckling.

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