CLINICAL CASES
431
GnRH: Gonadotropin-releasing hormone; a decapeptide containing an N-
terminal pyroglutaminyl residue and a C-terminal glycinamide residue.
GnRH is synthesized and secreted from the hypothalamus and binds
receptors on the anterior pituitary.
LH: Luteinizing hormone; a polypeptide hormone that is similar in struc-
ture to FSH and, like FSH, is synthesized and secreted from the anterior
pituitary in response to binding of GnRH. It binds to receptors on the
thecal cells of the ovarian follicle to increase synthesis of androgens.
When binding to receptors on the corpus luteum, it increases the syn-
thesis of progesterone.
Progesterone: A steroid hormone synthesized from cholesterol secreted
from the corpus luteum in the luteal phase of the menstrual cycle.
D ISC U SSIO N
With the onset of puberty, the normal menstrual (ovarian) cycle, as shown in
Figure 48-1, is initiated by the pulsatile release of gonadotropin-releasing
hormone (GnRH) from the hypothalamus. GnRH binds to plasma mem-
brane receptors in its target cells in the anterior pituitary and triggers acti-
vation of the phosphatidylinositol signaling pathway. This in turn signals the
pituitary to release both FSH and LH from the same cell. FSH binds its
plasma membrane receptor in the ovarian follicle to stimulate, via adeny-
late cyclase activation, cyclic AMP production and protein kinase A acti-
vation, increased ovarian synthesis and secretion of 17-P-estradiol, the female
sex hormone. This leads to maturation of the follicle and ovum. Estradiol also
induces progesterone receptors. Estrogens circulate in the bloodstream to
maintain female primary and secondary sex characteristics. The steroid hor-
mones estradiol and progesterone act by activating their intracellular receptors
(E2R and PR, respectively) to bind their response elements in promoter regions
of target genes. Together they promote the thickening and vascularization of
the uterine endometrium in preparation for implantation of the fertilized ovum.
Ovarian synthesis of inhibin, a negative feedback regulator of FSH (but not
LH) production, is also stimulated. As 17-b-estradiol levels reach a maxi-
mum, around day 13 of the cycle, they stimulate a massive release of LH and
to a lesser extent FSH, from the pituitary, known as the LH spike. The LH
spike, together with other factors such as prostaglandin F2a, triggers
ovulation.
After ovulation, estrogen biosynthesis by the follicle declines, leading to a
drop in blood levels of estrogen. The Graafian follicle now differentiates into
the corpus luteum, under the mediation of LH. LH binds plasma membrane
receptors in the corpus luteum, acting by the adenylate cyclase/protein kinase
A signaling pathway, to stimulate progesterone biosynthesis. The uterine
endometrial wall becomes secretory in preparation for implantation of the fer-
tilized egg. In the absence of fertilization, the corpus luteum dies, because of
decreased levels of LH. This leads to decreased production of progesterone
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