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a Abstracted from Tagatz, G. E., and Gurpide, E. (1973). Hormone secretion by the normal human ovary. In "Handbook of Physiology" (R. O. Greep and E. B. Astwood, eds.), Vol. II, Part I, Section 7, pp. 603-613. American Physiological Society, Bethesda, MD.

h Metabolic clearance rate (MCR) is an estimation of the rate at which the steroid is irreversibly removed from the plasma by inactivation (further metabolism). The plasma flow through the liver (a frequent site of steroid catabolism) is —1500 liters/day.

a Abstracted from Tagatz, G. E., and Gurpide, E. (1973). Hormone secretion by the normal human ovary. In "Handbook of Physiology" (R. O. Greep and E. B. Astwood, eds.), Vol. II, Part I, Section 7, pp. 603-613. American Physiological Society, Bethesda, MD.

h Metabolic clearance rate (MCR) is an estimation of the rate at which the steroid is irreversibly removed from the plasma by inactivation (further metabolism). The plasma flow through the liver (a frequent site of steroid catabolism) is —1500 liters/day.

the ovarian follicles and corpus luteum throughout the various phases of the human menstrual cycle. It is apparent that the actions of the gonadotropins, FSH and LH, have dramatic effects on the steroid-metabolizing enzymes of these tissues. In the plasma compartment, the estrogens are transported by a specific plasma protein, the steroid hormone-binding globulin (SHBG), and the progestins are transported by the plasma protein termed the corticosteroid-binding globulin (CBG). The biochemistry of CBG is described in Chapter 10, while SHBG is reviewed in Chapter 12. Both proteins effectively reduce the "free" concentration of both classes of steroids to on the order of 1-2%.

B. Peptide Hormones

As summarized in Table 13-1, a family of peptide hormones is associated with female reproduction. Those strictly associated with pregnancy and lactation, for example, human chorionic gonadotropin, prolactin, human placental lactogen, oxytocin, and relaxin, will be discussed in Chapter 14.

1. Gonadotropins

The chemistry of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) is discussed in detail in Chapter 5. Both FSH and LH are secreted by the adenohypophysis; their release is governed in a complex fashion by gonadotropin-releasing hormone

(GnRH), the blood level of circulating steroid hormones, and the interrelated actions of the gonadal regulatory peptides (inhibin, activin, and follistatin). The regulation of the secretion of FSH and LH as well as a description of their biological responses are given in Section IV.B.

The secretory functions of the pituitary gonado-tropes are controlled by the interaction of neural (CNS), local, and peripheral signals (see Figure 13-6 and Chapters 3 and 5). The decapeptide GnRH is secreted from the hypothalamus in a pulsatile fashion with short latency and is the primary stimulator of both LH and FSH. In addition, the steroid hormones, progesterone and estradiol, function as negative feedback signals at both the central and pituitary levels to diminish GnRH and gonadotropin release. The system is further modulated by three additional peptide hormones, inhibin, activin, and follistatin.

2. GnRH

The secretion of the gonadotropins FSH and LH by pituitary adenohypophysis is governed by the central nervous system (CNS) hypothalamus-mediated release of gonadotropin-releasing hormone (GnRH). GnRH is a decapeptide (see Figure 3-8) with an N-terminal pyroglutamyl residue and a C-terminal glyci-namide. Various chemically synthesized analogues of GnRH have been found to be useful in the clinical management of problems of female infertility and both female and male contraception.

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