Clinical Note

Gonadotropin Secretion and Antifertility Drugs

The negative feedback effects of estrogens and progesterone on gonadotropin secretion have been exploited to produce antifertility drugs. Chemical modifications that prolong their half-lives and enable them to escape destruction by the liver has made possible their administration by mouth. Preparations of estrogens alone, in combination with progestational compounds, or administered sequentially prevent follicular development by blocking gonadotropin secretion, thus preventing ovulation. Sequential administration of estrogens for 2 weeks followed by progestins and then withdrawal for a few days reproduces normal endometrial events, including menstruation. Depot injections of long-acting progestins can not only block ovulation by preventing the ovulatory surge of gonadotropin secretion but also stimulate production of dense cervical mucus, which prevents passage of sperm into the uterine cavity.

The beginning and end of cyclic ovarian activity (i.e., menarche and menopause) occur on a longer time scale. The events associated with the onset of puberty were considered in Chapter 45. Although we still do not know what biological phenomena signal readiness for reproductive development and the end of the juvenile period, it appears that the timekeeper for this process resides in the central nervous system, which initiates sexual development and function by activating the GnRH pulse generator. Termination of cyclic ovarian activity coincides with the disappearance or exhaustion of primordial follicles, but during the final decade of a woman's reproductive life there is a paradoxical doubling of the rate of loss of follicles by atresia. Aging of the GnRH pacemaker may be a factor in this acceleration of folli-cular loss, as studies in normally cycling women indicate that both the amplitude of LH pulses and the interval intervening between pulses increases with increased age.

Suggested Readings

Ackland JF, Schwartz NB, Mayo KE, Dodson RE. Nonsteroidal signals originating in the gonads. Physiol Revs 1992; 72:731-788.

Dorrington JH, Armstrong DT. Effects of FSH on gonadal function. Recent Prog Horm Res 1979; 35:301-332.

Giudice LC. Insulin-like growth factors and ovarian follicular development. Endocrine Rev 1992; 13:641-669.

Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocrine Rev 1996; 17:121-155.

Graham D, Clarke CL. Physiological action of progesterone in target tissues. Endocrine Rev 1997; 18: 502-519.

Hayes FJ, Crowley WF, Jr. Gonadotropinpulsations across development. Horm Res 1998; 49:163-168.

Knobil E, Hotchkiss J. The menstrual cycle and its neuroendocrine control, in: Knobil E, Neill JD, Eds., The physiology of reproduction, Vol. 2, 2nd ed., New York, Raven Press, 1994, pp. 711-749.

Marshall JC, Dalkin AC, Haisleder DJ, Paul SJ, Ortolano GA, Kelch RP. Gonadotropin-releasing hormone pulses: regulators of gonadotropin synthesis and ovarian cycles. Recent Prog Horm Res 1991; 47:155-187.

Matzuk MM. Revelations of ovarian follicle biology from gene knockout mice. Mol Cell Endocrinol 2000; 163:61-66.

McGee EA, Hsueh AJW. Initial and cyclic recruitment of ovarian follicles. Endocrine Rev 2000; 21:200-214.

Nilsson S, Makela S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M, Gustafsson JA. Mechanisms of estrogen action. Physiol Rev 2001; 81:1535-1565.

Richards JS, Jahnsen T, Hedin L, Lifka J, Ratoosh S, Durica JM, Goldring NB. Ovarian follicular development: from physiology to molecular biology. Rec Prog Horm Res 1987; 43:231-270.

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...

Get My Free Ebook

Post a comment