CHAPTER 25
The Gonads: Development & Function of the Reproductive System 401potency by markedly slowing their metabolism. The half-life
of human FSH is about 170 min; the half-life of LH is about 60
min. Loss-of-function mutations in the FSH receptor cause
hypogonadism. Gain-of-function mutations cause a sponta-
neous form of
ovarian hyperstimulation syndrome,
a condi-
tion in which many follicles are stimulated and cytokines are
released from the ovary, causing increased vascular perme-
ability and shock.
Human pituitary prolactin contains 199 amino acid resi-
dues and three disulfide bridges and has considerable struc-
tural similarity to human growth hormone and human
chorionic somatomammotropin (hCS). The half-life of pro-
lactin, like that of growth hormone, is about 20 min. Structur-
ally similar prolactins are secreted by the endometrium and
by the placenta.
RECEPTORS
The receptors for FSH and LH are G-protein coupled recep-
tors coupled to adenylyl cyclase through a stimulatory G pro-
tein (G
s
; see Chapter 2). In addition, each has an extended,
glycosylated extracellular domain.
The human prolactin receptor resembles the growth hor-
mone receptor and is one of the superfamily of receptors that
includes the growth hormone receptor and receptors for
many cytokines and hematopoietic growth factors (see Chap-
ters 2 and 3). It dimerizes and activates the Janus kinase/signal
transducers and activators of transcription (JAK–STAT) path-
way
and other intracellular enzyme cascades.
ACTIONS
The testes and ovaries become atrophic when the pituitary is
removed or destroyed. The actions of prolactin and the gona-
dotropins FSH and LH, as well as those of the gonadotropin
secreted by the placenta, are described in detail in succeeding
sections of this chapter. In brief, FSH helps maintain the sper-
matogenic epithelium by stimulating Sertoli cells in the male
and is responsible for the early growth of ovarian follicles in
the female. LH is tropic to the Leydig cells and, in females, is
responsible for the final maturation of the ovarian follicles and
estrogen secretion from them. It is also responsible for ovula-
tion, the initial formation of the corpus luteum, and secretion
of progesterone.
Prolactin causes milk secretion from the breast after estro-
gen and progesterone priming. Its effect on the breast involves
increased action of mRNA and increased production of casein
and lactalbumin. However, the action of the hormone is not
exerted on the cell nucleus and is prevented by inhibitors of
microtubules. Prolactin also inhibits the effects of gonadotro-
pins, possibly by an action at the level of the ovary. Its role in
preventing ovulation in lactating women is discussed below.
The function of prolactin in normal males is unsettled, but
excess prolactin secreted by tumors causes impotence.
REGULATION OF PROLACTIN SECRETION
The normal plasma prolactin concentration is approximately
5 ng/mL in men and 8 ng/mL in women. Secretion is tonically
inhibited by the hypothalamus, and section of the pituitary stalk
leads to an increase in circulating prolactin. Thus, the effect of
the hypothalamic prolactin-inhibiting hormone (PIH) dopa-
mine is normally greater than the effects of the various hypotha-
lamic peptides with prolactin-releasing activity. In humans,
prolactin secretion is increased by exercise, surgical and psy-
chologic stresses, and stimulation of the nipple (Table 25–3).
The plasma prolactin level rises during sleep, the rise starting af-
ter the onset of sleep and persisting throughout the sleep period.
Secretion is increased during pregnancy, reaching a peak at the
time of parturition. After delivery, the plasma concentration
falls to nonpregnant levels in about 8 days. Suckling produces a
prompt increase in secretion, but the magnitude of this rise
gradually declines after a woman has been nursing for more
than 3 months. With prolonged lactation, milk secretion occurs
with prolactin levels that are in the normal range.TABLE 25–3
Factors affecting the secretion
of human prolactin and growth hormone.Factor Prolactin
a
Growth
Hormone
aSleep I+ I+
Nursing I++ N
Breast stimulation in nonlactating women I N
Stress I+ I+
Hypoglycemia I I+
Strenuous exercise I I
Sexual intercourse in women I N
Pregnancy I++ N
Estrogens I I
Hypothyroidism I N
TRH I+ N
Phenothiazines, butyrophenones I+ N
Opioids I I
Glucose N D
Somatostatin N D+
L
-Dopa D+ I+
Apomorphine D+ I+
Bromocriptine and related ergot
derivatives D+ I
a
I, moderate increase; I+, marked increase; I++, very marked increase; N, no change;
D, moderate decrease; D+, marked decrease; TRH, thyrotropin-releasing hormone.