Female sex hormones

Ovaries
• The ovaries contain the female
germ cells (oocytes) and produce
hormones that are essential for
reproduction and development of
female sexual characteristics
 The major steroid hormones produced in the
ovary are as follows:
• (1) follicular or estrogenic
hormones, secreted by developing
Graaf follicle cells;
• (2) progestational hormone or
progesterone produced by the
corpus luteum formed in ovary
after follicle rupture at ovulation
• (3) androgenic hormones,
particularly androstenedione and
testosterone.
• Ovarian steroids synthesis is controlled by the pituitary gonadotropins
LH and FSH.
• In addition, the ovary produces peptidic hormones
• relaxin, secreted by the corpus luteum during pregnancy
• activin and inhibin, which are found in the follicular fluid.
OVARIAN HORMONES
• Estrogen
• Progesterone
• Androgens
Estrogens
• These hormones are synthesized in
granulosa and antral follicular cells.
• They differ from all other steroids by
an aromatic A ring and the absence of
carbon 19 at C10 (C10 has a methyl
group).
• The estrogens produced in ovary are
estradiol and estrone, both are
interconvertible.
Progesterone
• This hormone is produced in all
steroidogenic ovary cells, especially in
the corpus luteum that develops after
the rupture of the follicle during
ovulation.
• It is also produced in the placenta,
particularly in late pregnancy, and in the
adrenal cortex, as an intermediate
metabolite in corticosteroids synthesis
Androgens
• Androstenedione and testosterone are produced mainly in interstitial
cells and thecal cells of the ovary.
Biosynthesis and metabolism.
• The precursor of all ovarian steroidal hormones is cholesterol.
• Although a small proportion of cholesterol used by the ovary is
synthesized locally, most of it is taken up from the blood, through
endocytosis of LDL.
• Cholesterol released into the lysosomes is sent to the mitochondria
by the StAR (Steroidogenic acute regulatory protein).
• The synthesis of steroids in the ovary initially leads to the formation of
androstenedione and testosterone, following reactions identical to those
described for the testis.
• Estrogens are primarily metabolized
in the liver; the C17 ketone function
is reduced to−OH and a hydroxyl
group is added to C16.
• The resulting compound, called
estriol,is the main estrogen
metabolite eliminated by urine,
conjugated with sulfate or
glucuronate.

• The major progesterone metabolites

are pregnandiol and pregnanetriol,
excreted as glucuronide conjugates.
Mechanism of action
• All steroids share similar mechanisms of action.
• They cross the plasma membrane and reach their receptors in the
nucleus of the target cells.
• There steroids form hormone-receptor complexes, in which HSPs are
also involved.
• Two types of estrogen receptors, α and β, exist.
• They differ in their tissue distribution and function.
• The β receptor can modulate the activity of the α receptor.
Estrogen actions
• Estrogens decreasing glucose tolerance, reducing plasma cholesterol
concentration, and increasing HDL levels.
• They stimulate the liver synthesis of transport proteins for thyroid and sex
hormones, and transcortin.
• They promote bone growth and epiphyseal closure at puberty, and inhibit
osteoclast activity.
• In adult women, estrogens participate in bone remodeling, and play a
crucial role in the maintenance of bone mass.
• The rapid decrease in estrogen secretion, common in postmenopausal
women, is an important factor that contributes to osteoporosis.
Nongenomic actions
• Estradiol also exerts effects that are not mediated by the nuclear
receptor.
• For example, estradiol causes rapid increase in intracellular calcium
concentration [Ca2+]i in endometrium, maturing oocytes, and
granulosa cells.
• It also has direct action on the vascular system, and activates nitric
oxide synthesis and produces vasodilation.
Metabolic effects
• Estrogens have anabolic action in female genital organs.
• They increase the uptake of water, sodium, amino acids, and glucose
by the myometrium.
• These actions are secondary to stimulation of protein synthesis
Effects on genital organs
• Estrogens stimulate the development of
the ovary, Fallopian tubes, and uterus.
• Estrogens stimulate uterine growth and
prepare the uterine lining for the action
of progestational hormones.
• They induce endometrial development
and increase its vascularization.
• They produce characteristic changes in
the Fallopian tubes and the vaginal
epithelium, and are responsible for the
development and maintenance of the
female secondary sexual characteristic
Progesterone Actions
• Progesterone appears in blood after ovulation.
• It favors the endometrium development and prepares the uterus to receive
the embryo.
• High levels of progesterone are important not only to facilitate
implantation, but also to maintain pregnancy, stimulating uterine growth,
and opposing the action of factors that favor myometrium contraction.
• In the mammary gland, progesterone activates the development of acini,
preparing the gland for milk production.
• Progesterone is responsible for the rise in basal body temperature that
occurs during the second half of the menstrual cycle
• Progesterone derivatives have been developed and are used as
contraceptives
Metabolic effects.
• Progestagens have nonspecific effects, mimicking those of
glucocorticoids.
• Although this effect is minor, they mobilize tissue proteins for use in
liver gluconeogenesis.
• Progesterone acts as a competitive inhibitor of aldosterone in the
kidney and has natriuretic action.
Oral contraceptives
• Estrogens repress FSH secretion, provide stability, and increase the
number of progesterone receptors in the endometrium.
• Progestagens, in pharmacological doses, inhibit ovulation by
suppressing GnRH (Gonadotropin releasing hormone) pulses and LH
release, prevent egg implantation, and induce production of very
thick cervical mucus that hinders sperm penetration
OVARIAN PEPTIDE HORMONES
• Relaxin
• Inhibin
• Activin
• Follistatin
• Relaxin. This hormone is produced in the
corpus luteum during pregnancy.
• Its production is stimulated by chorionic
gonadotropin.
• It is composed by two peptide chains
linked by disulfide bridges.
• Its structure is similar to that of insulin.
• Relaxin inhibits uterine motility and
favors reproductive tract structures
relaxation during gestation.
• Inhibins. These hormones were isolated from follicular fluid; they are
produced predominantly in the preovulatory follicle and corpus
luteum of primates.
• It is a heterodimer of α and β chains.
• They exert inhibitory control of the secretion of FSH in the pituitary
gland.
• Together with follistatin, they oppose to activin action.
• The balance activin/inhibin changes during follicle development;
activin prevails during the earliest stages, while inhibin predominates
at later stages.
• Activins. These hormones are
homodimers of β chains
similar to those of inhibin, but
with opposite functional
properties.
• GnRH stimulates activin
synthesis which, in turn,
selectively activates FSH
secretion.
• Primarily, activins exert
paracrine action within the
ovary, where it increases FSH-
receptor gene expression.
• There is evidence suggesting a
role of activin in cell
differentiation processes.
• Follistatins. These hormones
are 40 kDa protein
• Produced in follicular cells
that bind activin with high
affinity and neutralize its
biological activity.