Ovarian Hormones

The principal hormones secreted by the ovary are estrogens (estradiol-17fi and estrone) and progesterone. These hormones are steroids and are derived from cholesterol by the series of reactions depicted in Fig. 6. Their biosynthesis is intricately interwoven with the events of the ovarian cycle. In addition, the ovary produces a large number of biologically active peptides, most of which act within the ovary as paracrine growth factors, but at least two, inhibin and relaxin, are produced in sufficient amounts to enter the blood and produce effects in distant cells.


Unlike humans, who, it has been said, ''eat when they are not hungry, drink when they are not thirsty, and make love at all seasons of the year,'' most vertebrate animals mate only at times of maximum fertility of the female. This period of sexual receptivity is called estrus, derived from the Greek word for vehement desire. Estrogens are compounds that promote estrus and were originally isolated from the follicular fluid of sow ovaries. Characteristic of steroid-secreting tissues, little hormone is stored within the secretory cells themselves. Estrogens circulate in blood loosely bound to albumin and tightly bound to the testosterone-estradiol-binding globulin (TeBG), which is also called the sex-hormone-binding globulin (SHBG; see Chapter 45). Plasma concentrations of estrogens are considerably lower than those of other gonadal steroids and vary over an almost 20-fold range during the cycle.

Liver is the principal site of metabolic destruction of the estrogens. Estradiol and estrone are completely cleared from the blood by a single passage through the liver and are inactivated by hydroxylation and conjugation with sulfate and glucuronide. About halfthe protein-bound estrogen in blood is conjugated with sulfate or glucuronide. Conjugated estrogens excreted in the bile are reabsorbed in the lower gut and returned to the liver in portal blood in a typical enterohepatic circulatory pattern. The kidney is the chief route of excretion of estrogenic metabolites.


Pregnancy, or gestation, requires the presence of another ovarian steroid hormone, progesterone. In the nonpregnant woman, progesterone secretion is largely confined to cells of the corpus luteum, but, because it is an intermediate in the biosynthesis of all steroid hormones, small amounts may also be released from the adrenal cortex. Some progesterone is also produced by granulosa cells just before ovulation. The rate of progesterone production varies widely. Its concentration in blood ranges from virtually nil during the early preovu-latory part of the ovarian cycle to as much as 2 mg/dL after the corpus luteum has formed. Progesterone circulates in blood in association with plasma proteins and has a high affinity for the corticosteroid-binding globulin (CBG). Liver is the principal site of progesterone inactivation, which is achieved by reduction of the A ring and the keto groups at carbons 3 and 20 to give pregnanediol, which is the chief metabolite found in urine. Considerable degradation also occurs in the uterus.


As discussed in Chapter 45, inhibin is a 32-kDa disulfide-linked dimer of an a subunit and either of two p subunits, pA or pB and enters the circulation as either inhibin A (a/pA) or inhibin B (a/pB). Expression of the pA subunit is greatest in luteal cells, while expression of the pB subunit is a product of granulosa cells. Consequently, blood levels of inhibin B are highest during the periods of preovulatory growth and expansion of granulosa cells, while blood levels of inhibin A are highest during peak luteal cell function. In addition to serving as a circulating hormone, inhibin probably exerts paracrine actions in the ovary, and activin formed by dimerization of two p subunits also exerts important intraovarian paracrine actions. The activin-binding peptide follistatin, which blocks activin action, also plays an important intraovar-ian role. Although some activin is found in the circulation, its concentrations do not change during the ovarian cycle, and its source is primarily extra-ovarian.


The corpus luteum also secretes a second peptide hormone called relaxin, which was named for its ability to relax the pubic ligament of the pregnant guinea pig. In other species, including humans, it also relaxes the myometrium and plays an important role in parturition by causing softening of the uterine cervix. Its peptide structure, particularly the organization of its disulfide bonds places it in the same family as insulin and the insulin-like growth factors (IGFs). A physiological role for relaxin in the nonpregnant woman has not been established.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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