Ganong's Review of Medical Physiology, 23rd Edition

420 SECTION IVEndocrine & Reproductive Physiology

Relaxin

Relaxin is a polypeptide hormone that is produced in the cor-
pus luteum, uterus, placenta, and mammary glands in women
and in the prostate gland in men. During pregnancy, it relaxes
the pubic symphysis and other pelvic joints and softens and
dilates the uterine cervix. Thus, it facilitates delivery. It also in-
hibits uterine contractions and may play a role in the develop-
ment of the mammary glands. In nonpregnant women,
relaxin is found in the corpus luteum and the endometrium
during the secretory but not the proliferative phase of the
menstrual cycle. Its function in nonpregnant women is un-
known. In men, it is found in semen, where it may help main-
tain sperm motility and aid in sperm penetration of the ovum.
In most species there is only one relaxin gene, but in humans
there are two genes on chromosome 9 that code for two struc-
turally different polypeptides that both have relaxin activity.
However, only one of these genes is active in the ovary and the
prostate. The structure of the polypeptide produced in these
two tissues is shown in Figure 25–30.

CONTROL OF OVARIAN FUNCTION

FSH from the pituitary is responsible for the early maturation
of the ovarian follicles, and FSH and LH together are responsi-
ble for their final maturation. A burst of LH secretion (Figure
25–25) is responsible for ovulation and the initial formation of
the corpus luteum. A smaller midcycle burst of FSH secretion
also occurs, the significance of which is uncertain. LH stimu-
lates the secretion of estrogen and progesterone from the cor-
pus luteum.

Hypothalamic Components

The hypothalamus occupies a key position in the control of
gonadotropin secretion. Hypothalamic control is exerted by

GnRH secreted into the portal hypophysial vessels. GnRH

stimulates the secretion of FSH as well as LH.

GnRH is normally secreted in episodic bursts, and these

bursts produce the circhoral peaks of LH secretion. They are

essential for normal secretion of gonadotropins. If GnRH is

administered by constant infusion, the GnRH receptors in the

anterior pituitary down-regulate and LH secretion declines to

zero. However, if GnRH is administered episodically at a rate of

one pulse per hour, LH secretion is stimulated. This is true even

when endogenous GnRH secretion has been prevented by a

lesion of the ventral hypothalamus.

It is now clear not only that episodic secretion of GnRH is a

general phenomenon but also that fluctuations in the frequency

and amplitude of the GnRH bursts are important in generating

the other hormonal changes that are responsible for the men-

strual cycle. Frequency is increased by estrogens and decreased

by progesterone and testosterone. The frequency increases late

in the follicular phase of the cycle, culminating in the LH surge.

During the secretory phase, the frequency decreases as a result

of the action of progesterone (Figure 25–31), but when estro-

gen and progesterone secretion decrease at the end of the cycle,

the frequency once again increases.

At the time of the midcycle LH surge, the sensitivity of the

gonadotropes to GnRH is greatly increased because of their

FIGURE 25–30 Structure of human luteal and seminal
relaxin. Pca, pyroglutamic acid. (Modified and reproduced with permission
from Winslow JW et al: Human seminal relaxin is a product of the same gene as
human luteal relaxin. Endocrinology 1992;130:2660. Copyright © 1992 by The
Endocrine Society.)

LeuPca

Leu

Leu

Leu

Ser Ser

Ser

Ser

Ser

Ala

Ala

Ala

Asn

Tyr

Leu

Lys

Lys

LysArg

Arg

Arg ArgAla

Gly Ala

GlnIle Ile

Ile Phe

Cys

Cys

Cys

HisVal

Val

Val Gly

Glu

Glu

Glu

Gly

Met

Met

Cys

Cys

Cys

Thr

Thr

Trp

Trp

Asp

SS

COO−

COO−

A5 A1

A10 A15

A20

A24 B25

B29

B15 B20

B10

B5

B1

NH 3

S

S

SS

FIGURE 25–31 Episodic secretion of LH (s) and FSH (d)

during the follicular stage (top) and the luteal stage (bottom) of

the menstrual cycle. The numbers above each graph indicate the

numbers of LH pulses per 12 hours and the plasma estradiol (E 2 ) and

progesterone (P) concentrations at these two times of the cycle.

(Reproduced with permission from Marshall JC, Kelch RO: Gonadotropin-releasing

hormone: Role of pulsatile secretion in the regulation of reproduction. N Engl J Med

1986;315:1459.)

0

4

8

12

16

(7.5/12h) P

0

4

8

12

16

20

8

PM

12

AM

4

PM

8

AM

Time

LH ( ), FSH ( ) mlU/mL

98 pg/mL

0.4 ng/mL

LH pulse E 2

(4/12h) P

192 pg/mL

20 ng/mL

LH pulse E 2