Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communications
Sex Gland Hormones
Phenotypic Sex

Internal Reproductive Structures

Male Sex Hormones are directly involved in the Differentiation of the primary duct system (the Wolffian and Müllerian ducts) and the primordia of the external genitalia. The male internal reproductive Organs develop from the primary Wolffian ducts, while the female organs develop from the Müllerian ducts (Fig. 50.11).

Whether the Wolffian or Müllerian ducts develop in the embryo depends on The production of a specific testicular factor known as Müllerian-inhibiting substance (MIS) or Müllerian-inhibiting factor (MIF). This factor is a glycoprotein with a Molecular Weight of 70,000. It is produced by the seminiferous tubules and represents the first endocrine function of the Testes. The mechanism by which MIS suppresses Müllerian duct development remains unclear, but it is evidently an active process unrelated to the subsequent action of testosterone.

External Genitalia

The type of external genitalia that develops from the bipotential primordium is determined by the presence or absence of another testicular hormone—testosterone and its derivative, dihydrotestosterone (DHT).

The synthesis of testosterone is the process that directly precedes fetal masculinization. In male rabbit embryos, testosterone synthesis begins at 17–17.5 days of age; it is associated with a sharp increase in the levels of the Cholesterol side-chain Cleavage enzyme, as well as the 3β-hydroxysteroid dehydrogenase/∆5,4-isomerase enzyme complex (Key Enzymes in testosterone Biosynthesis). Other steroidogenic enzymes are consistently present in the embryonic Gonads. Estrogen synthesis in the Ovaries begins at the same time as testosterone synthesis. This coincidence apparently indicates that female sexual differentiation is not entirely a passive process, as estrogen synthesis by immature gonads could play a role in stimulating the division of primordial Germ Cells or their differentiation into oogonia. The signal that triggers steroidogenesis has not been identified, nor is it known whether this process is regulated by Other Hormones during early stages. At later stages of Embryogenesis, as in postnatal life, steroidogenesis is regulated by LH, which influences The rate of cholesterol side-chain cleavage.

Prior to the discovery of DHT, it was believed that The Development of the male reproductive tract depended solely on testosterone. The fact that DHT is also required for this process was established through experiments with embryonic Tissues. It was demonstrated that immediately before the onset of masculinization, 5a-reductase activity is highest in the anlagen of the Prostate Gland and external genitalia, whereas this enzyme cannot be detected in the Wolffian ducts at that time. These findings were confirmed by genetic studies identifying individuals lacking 5a-reductase activity. Such individuals, despite being genetic males with normal Wolffian structures, exhibit a female phenotype with one exception: their Vagina is incompletely developed.

Class="center">References

General

Huggins С. Two principles in endocrine therapy of Cancer. Hormone deprival and hormone Interference, Cancer Res., 1965, 25, 1163.

Ohno S., Geller L. N.. Lai E. V. Y. Tfm mutation and masculinization versus feminization on the mouse Central Nervous system. Cell, 1974, 3, 235.

O’Malley B. W. Steroid hormone action in Eukaryotic cells, J. Clin. Invest., 1984, 74, 307.

Testicular Hormones

Hall P. F. Gonadotropic Regulation of Testicular function, Pages 1511—1519. In: The Androgens of the Testis, EikNes К. B. (ed.), Dekker, 1970.

Hall P. F. Testicular hormones: Synthesis and control. Pages 1511 -1520. In: Endocrinology, Vol. 3, DeGroot L. J. (ed), Grune and Stratton, 1979.

Longcope C., Kato T., Horton R. Conversion of Blood androgens to estrogen in normal men and women, J. Clin. Invest., 1969, 48, 2191.

Mainwaring W. I. P. The MECHANISM OF ACTION of Androgens, Springer, 1977.

Samuels L. T., Matsumoto K. Localization of enzymes involved in testosterone biosynthesis by the mouse testis, Endocrinology, 1974, 94, 55.

Wilson J. METABOLISM of testicular androgens, Chap. 25, pp. 491-508. In: Handbook of Endocrinology, Section 7; Endocrinology, Vol. 5: Male Reproductive System. Hamilton D. W., Grcep R. O. (ed.). American Physiological Society, Washington DC, 1975.

Ovarian Hormones

Channing С. P., Coudert S. P. The Role of granulosa cells and follicular fluid in estrogen secretion by the monkey Ovary in vivo, Endocrinology, 1976, 98, 590.

Channing C.P., Tsafriri A. Mechanism of action of luteinizing hormone and follicle-stimulating hormone on the ovary in vitro. Metabolism, 1977, 26, 413.

Green S. et al. Human estrogen receptor DNA: Sequence, expression and Homology to v-erh-A, Nature, 1986, 320. 134.

Jensen E. V., Jacobson H. I. Basic guides to The Mechanism of estrogen action, Recent Prog. Horm. Res., 1962, 18, 387.

Siiteri P. K., Febres F. Ovarian hormone synthesis, Circulation and Mechanisms of action, Pages 1401-1417. In: Endocrinology, Vol. 3, DeGroot L. J. (ed.), Grume and Statton, 1979.

Toft D., Górski J. A receptor molecule for estrogens. Proc. Natl. Acad. Sci. USA, 1966. 55. 1574.

Sex differentiation

Bullock L. P., Barden C. W., Ohno S. The androgen insensitive mouse: Absence of intranuclear androgen retention in the Kidney, Biochem. Biophys. Res. Commun., 1971,44, 1537.

Jost A. et al. Studies in sex differentiation in mammals, Recent Prog. Horm. Res., 1973, 29, 1.

Ohno S. Major regulatory genes for mammalian sexual development, Cell, 1976. 7, 315.

Ohno S. The role of H-Y antigen in primary Sex Determination, JAMA, 1978, 239. 217.

Wilson J. D., Walker J. D. The conversion of testosterone to 5a- androsten-17ß-ol-3-one (dihydrotestosterone) by Skin slices of man, J. Clin. Invest., 1969, 48, 371.

Wilson J. D. et al. The endocrine control of male phenotypic development, Aust. J. Biol. Sci., 1983, 36, 101.



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