Other Ovarian Hormones

OTHER OVARIAN HORMONES

The normal ovary produces small amounts of androgens, includ-ing testosterone, androstenedione, and dehydroepiandrosterone. Of these, only testosterone has a significant amount of biologic activity, although androstenedione can be converted to testoster-one or estrone in peripheral tissues. The normal woman produces less than 200 mcg of testosterone in 24 hours, and about one third of this is probably formed in the ovary directly. The physiologic significance of these small amounts of androgens is not estab-lished, but they may be partly responsible for normal hair growth at puberty, for stimulation of female libido, and, possibly, for metabolic effects. Androgen production by the ovary may be markedly increased in some abnormal states, usually in association with hirsutism and amenorrhea as noted above. The ovary also produces inhibin and activin. These peptides consist of several combinations of α and β subunits and are described in greater detail later. The αβ dimer (inhibin) inhibits FSH secretion while the ββ dimer (activin) increases FSH secre-tion. Studies in primates indicate that inhibin has no direct effect on ovarian steroidogenesis but that activin modulates the response to LH and FSH. For example, simultaneous treatment with activin and human FSH enhances FSH stimulation of progesterone synthesis and aromatase activity in granulosa cells. When combined with LH, activin suppressed the LH-induced progesterone response by 50% but markedly enhanced basal and LH-stimulated aromatase activity. Activin may also act as a growth factor in other tissues. The physiologic roles of these modulators are not fully understood.

Relaxin is another peptide that can be extracted from theovary. The three-dimensional structure of relaxin is related to that of growth-promoting peptides and is similar to that of insulin. Although the amino acid sequence differs from that of insulin, this hormone, like insulin, consists of two chains linked by disulfide bonds, cleaved from a prohormone. It is found in the ovary, pla-centa, uterus, and blood. Relaxin synthesis has been demonstrated in luteinized granulosa cells of the corpus luteum. It has been shown to increase glycogen synthesis and water uptake by the myometrium and decreases uterine contractility. In some species, it changes the mechanical properties of the cervix and pubic liga-ments, facilitating delivery.

In women, relaxin has been measured by immunoassay. Levels were highest immediately after the LH surge and during menstruation. A physiologic role for this peptide has not been established.

Clinical trials with relaxin have been conducted in patients with dysmenorrhea. Relaxin has also been administered to patients in premature labor and during prolonged labor. When applied to the cervix of a woman at term, it facilitates dilation and shortens labor.

Several other nonsteroidal substances such as corticotropin-releasing hormone, follistatin, and prostaglandins are produced by the ovary. These probably have paracrine effects within the ovary.