The two types of ovarian sex hormones are the estrogens and the progestins. By far the most important of the estrogens is the hormone estradiol, and by far the most important progestin is progesterone. The estrogens mainly promote proliferation and growth of specific cells in the body and are responsible for development of most secondary sexual characteristics of the female. On the other hand, the progestins are concerned almost entirely with final preparation of the uterus for pregnancy and the breasts for lactation.
Chemistry Of The Sex Hormones
The Estrogens. In the normal nonpregnant female, estrogens are secreted in major quantities only by the ovaries, though minute amounts are also secreted by the adrenal cortices. In pregnancy, tremendous quantities are also secreted by the placenta.
Only three estrogens are present in significant quantities in the plasma of the human female: β-estradiol,estrone, and estriol. The principal estrogen secreted by the ovaries is β-estradiol. Small amounts of estrone are also secreted, but most of this is formed in the peripheral tissues from androgen secreted by the adrenal cortices and by the ovarian thecal cells. Estriol is a very weak estrogenic oxidative product derived from both estradiol and estrone, the conversion occuring mainly in the liver.
The estrogenic potency of β -estradioll is 12 times that of estrone and 80 times that of estriol. Considering these relative potencies, one can see that total estrogenic effect of β -estradiol is usually many times that of the other two together. For this reason β -estradiol is considered to be the major estrogen, though the estrogenic effects of estrone are far from negligible.
The Progestins. By far the most important of the progestins is progesterone. However, small amounts of another progestin, 17-a-hydroxyprogesterone, also are secreted along with progesterone and have essentially the same effects. Yet for practical purposes it is usually proper to consider progesterone to be the single important progestin.
In the normal nonpregnant female, progesterone is secreted in significant amounts only during the latter half of each ovarian cycle, when it is secreted by the corpus luteum. Only minute amounts of progesterone appear in the plasma during the first half of the ovarian cycle, secreted approximately equally by the ovaries and the adrenal cortices. Yet, as we shall see in the following chapter, very large amounts of progesterone are also secreted by the placenta during pregnancy, especially after the fourth month of gestation.
Synthesis Of The Estrogens And Progestins.
Note from the chemical formulas of the estrogens and progesterone, all of these are steroids. They are synthesized in the ovaries mainly from cholesterol derived from the blood, but to a slight extent also from acetyl coenzyme A, multiple molecules of which can combine to form the appropriate steroid nucleus. During synthesis, progesterone and the male sex hormone testosterone are mainly synthesized first; then, during the follicular phase of the ovarian cycle, before these can leave the ovaries, almost all the testosterone and much of the progesterone are converted into estrogens by the granulosa cells. During the luteal phase of the cycle, far too much progesterone is formed for all of it to be converted, which accounts for the large progesterone secretion at this time. Even so, about one-fifteenth as much testosterone is secreted into the plasma of the female by the ovaries as is secreted into the plasma of the male by the testes.
Transport Of Estrogens And Progesterone In The Blood.
Estrogens and progesterone are both transported in the blood bound mainly with plasma albumin and specific the binding between these hormones and the plasma proteins is loose enough that they are rapidly released to the tissues over a period of 30 minutes or so.
Fate Of The Estrogen; Function Of The Liver In Estrogen Degradation.
The liver conjugates the estrogens to form glucuronides and sulfates, and about one fifth of these conjugated products are excreted in the urine. Also, the liver converts the potent estrogens estradiol and estrone into the almost totally impotent estrogen estriol. Therefore, diminished liver function actually 'increases' the activity of estrogens in the body, sometimes causing 'hyperestrinism'.
Fate Of Progesterone.
Within a few minutes after secretion, almost all the progesterone is degraded to other steroids that have no progesteronic effect. Here, as is also true with the estrogens, the liver is especially important for this metabolic degradation.
The major end product of progesterone degradation is 'pregnanediol'. Approximately 10 per cent of the original progesterone is excreted in the urine in this form. Therefore, one can estimate the rate of progesterone formation in the body from the rate of this excretion.
