gonad hormones : female prof.dr.gülden burçak 2011-2012
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Gonad Hormones : Gonad Hormones : FemaleFemale
Prof.Dr.Gülden BurçakProf.Dr.Gülden Burçak
2011-20122011-2012
Ovary : produces female sex Ovary : produces female sex hormones and female germ hormones and female germ
cellscells
The ovarian follicles are of two functional types; nongrowing ( primordial) and growing
Primordial follicles degenerate (atresia) Mature ovarian follicle (graafian) consists three
layers of cells : theca externa, theca interna and granulosa
The oocyte is contained within the follicular fluid After rupture of the mature follicle and release of
the ovum, granulosa and theca cells proliferate to form the corpus luteum.
Corpus luteum is a transient endocrine organ
Hypothalamic-Pituitary-Ovarian Axis
Constant pulsatile release of GnRH from the hypothalamus
Synthesis, storage and secretion of gonadotropins (FSH and LH) from the anterior pituitary
(-/+)Feedback relationships between the ovarian hormones (estradiol,progesterone) , GnRH, FSH and LH secretions
Cyclical ovarian function
(+) Feedback of gonadal steroids on pituitary
E2 > 700 pmol/L,maintenance of elevated levels for at least 48 hours
Progesterone, only after the pituitary has been exposed to prolonged high levels of E2
Chronic stress or profound weight loss can disrupt the pattern of GnRH secretion and lead to anovulation and amenorrhea.
In childhood : HPA remains highly sensitive to (-) feedback effects of gonadal steroids
In puberty : adrenarche, decreased sensitivity of HPA to (-) feedback and gonadarche, increased E2, onset of ovulatory cycles
androstenedione,DHEA, DHEAS: 6-8 years pulsatile secretion of GnRH is critical in the
initiation of puberty. in girls FSH increases earlier than LH
Ovarian steroid hormones Estrogens C18 (Granulosa) 17 ß-Estradiol Estrone : post-menopause Estriol : in pregnancy Progestagens C21 (Corpus Luteum) Pregnenolone Progesterone 17 OH Progesterone Androgens C19 (Theca) DHEA, androstendione, testosterone,
dihydrotestosterone
Aromatization of androgens in granulosa cells (also some estradiol in corpus luteum)
Three hydroxylation steps, O2 and NADPH P450 mixed-function oxidase Testosterone estradiol Androstendione estrone Peripheral aromatization of androgens Adrenal androgens : DHEA (major but weak),
androstendione (potent) Conversion : 3β-hydroxy steroid dehydrogenase,Δ5,4
isomerase During pregnancy and post-menopausal period In adipose cells, liver, skin and other tissues Increased aromatase activity , estrogenization in
cirrhosis,hyperthyroidism, aging and obesity
Ovarian nonsteroidal hormones
Cytokines, growth factors and neuropeptides Inhibins : multifunctional glycoproteins A and B Inhibin A(αßA) is low in early follicular phase, high in the
luteal phase ;inhibin B(αßB) parallels FSH Inhibin B synthesized in granulosa cells and inhibin A in
corpus luteum cells. increase theca cell androgen production Ovarian-pituitary negative feedback relationships Activins : disulfide-linked dimers of the ß-subunits of
inhibin. Activin A produced in the ovary augments the effects of
FSH Activin B produced in the gonadotropes increases FSH
secretion
60% loosely bound to albumin (>3000mg/L) 38% bound with high affinity to SHBG % 2-3 is free Progesterone binds strongly to CBG and
weakly to albumin The binding proteins provide a circulating
reservoir of hormone The metabolic clearance rates are inversely
related to SHBG affinity Conjugated derivatives are not bound
SHBG synthesis in hepatocytes
Increased by thyroid hormones, estrogens (5-10x),decreased levels of androgens,high carbohydrate diet, stress, aging, cirrhosis.
Decreased by androgens (2x) hyperprolactinemia, increased growth hormone, obesity, menopause, progestins, glucocorticoids.
The normal level of SHBG is about 30-50% lower in men than in women.
Metabolism of ovarian steroids
In the liver,estradiol (E2) and estrone(E1 ) are converted to estriol (E3) and conjugated with glucuronic a. or sulfate; excreted by the kidney
Oral estrogens are effective because the activity of conjugating enzymes are low
Progesterone is converted to pregnanediol, conjugated (sodium pregnanediol-20 glucuronide) and excreted by the kidney
Some synthetic steroids have progestational activity and avoid hepatic metabolism;used as contraceptives
Estrogens
Maturation of primordial germ cells Provision of the hormonal timing for
ovulation Developing the tissues that will allow for
implantation of the blastocyt Establishment of the milieu required for
the maintenance of pregnancy Provision of the hormonal influences for
parturition and lactation Anabolic effects on bone and cartilage Vasodilation and heat dissipation
Progestins generally require the previous or concurrent
presence of estrogens reduce the proliferative activity of the estrogens
on the vaginal epithelium convert the uterine epithelium from proliferative
to secretory ; preparing it for implantation of the fertilized ovum.
enhance the development of the acinar portions of breast glands after estrogens have stimulated ductal development.
decrease peripheral blood flow, decrease heat loss
Menstrual cycle-Follicular phase
A particular follicle begins to enlarge under the influence of FSH
E2 and LH rise, E2 reaches its max. level 24 hours before the LH (FSH) peak and sensitizes the pituitary to GnRH
LH peak heralds the end of the follicular phase and precedes ovulation by 16-18 hours.
Follicle rupture ,releasing an ova Continual administration of high doses of
estrogen (oral contraceptives) supresses LH and FSH release and inhibits the action of GnRH on the pituitary
Menstrual cycle-Luteal phase
The granulosa cells of the ruptured follicle luteinize and form the corpus luteum
Corpus luteum produces progesterone and some E2 Estradiol peaks about midway through the luteal phase
and then declines to a very low level.The major hormone is progesterone
LH is required for the early maintenance of the corpus luteum and the pituitary supplies it for 10days.
If implantation occurs LH function is assumed by hCG hCG stimulates progesterone synthesis by corpus
luteum until placenta begins to make in large amounts In the absence of implantation corpus luteum regresses
causing a decrease in progesterone.
Placental hormones maintain pregnancy
Human chorionic gonadotropin hCG structurally similar to LH supports corpus luteum until placenta produces sufficient
amounts of progesterone Progestins 6-8 weeks : corpus luteum produces progesterone thereafter : placenta produces progesterone (30-40 times
more) Placenta does not synthesize cholesterol and depends on
maternal supply Estrogens E1, E2, E3 The major hormone is E3 synthesized by feto-placental
function Placental lactogen (PL): chorionic somatomammotropin/
placental growth hormone
Steroid metabolism by the fetal-Steroid metabolism by the fetal-maternal unitmaternal unit
Mammary gland development
E2 (for ductal growth) Progesterone (alveolar proliferation) Additional actions of prolactin,
glucocorticoids, insulin Progesterone inhibits milk production and
secretion in late pregnancy Lactation : prolactin and oxytocin The production of oxytocin and it’s
receptors are stimulated by estrogens and inhibited by progesterone
Menopause
Weak estrogen ,E1, produced by aromatization of androstenedione
Marked increases of LH and FSH Estrone is not always able to prevent
the atrophy of secondary sex tissues and osteoporosis
Pathological States Hypogonadism Gonadal dysgenesis Polycystic ovary syndrome : overproduction of
androgens ( hirsutism, obesity,irregular menses,impaired fertility)
Hypergonadism Granulosa-theca cell tumors Persistent trophoblastic tissue : benign
hydatiform mole and its malignant form , choriocarcinoma
Infertility Elevated testosterone,decreased SHBG DHEA sulphate :adrenal ;androstenedione : ovary
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