Androgenic control of nucleic acid and protein synthesis in male accessory genital organs.

A survey is given of experimental studies on the influence of treatment with androgenic hormones in vivo on various intermediary reactions involved in ribonucleic acid (RNA) and protein synthesis in the prostate gland and seminal vesicle, with particular reference to the control of the growth and functional differentiation of these organs by testosterone and related steroids. Studies on the influence of androgens on RNA metabolism and protein biosynthesis in mouse kidney, certain muscles, and some other extragenital tissues are also considered. An ever-increasing amount of experimental effort has been expended over the last 5 years toward examining various intermediate reactions involved in ribonucleic acid and protein synthesis in male accessory genital glands. Much of this work has been carried out vis-a-vis the allembracing effects of androgens on the growth and functional differentiation of these organs. The strategy and tactics of these researches have often resembled those employed in comparable investigations on the action of estrogenic hormones on various structures in the female genital tract. (Comparatively little attention has been given to the nature and chronology of molecular events that underlie the biological actions of gestagens.) The remarkable progress in our understanding of the role of various forms of ribonucleic acid in gene expression and protein synthesis, together with the failure of many attempts to explain the action of sex hormones in terms of their direct effects on either isolated enzyme systems or on the permeability of cell or organelle membranes, has naturally focused attention on the sex hormonal control of the synthesis and turnover of specific enzymes and structural proteins. Before considering some phenomenological details of these processes in the male reproductive tract, it may be well to list certain aspects of the chemical physiology of androgens and estrogens which must ultimately be taken into account by any J. CELL. AND COMP. PHYSIOL., 66: 111-124. comprehensive molecular theories of sex hormone action. ( 1 ) It is well established that common pathways exist for the biosynthesis of androgens and estrogens in the ovary, testis, adrenal cortex, and placenta. These two categories of sex hormones can be elaborated in the aforementioned steroid factories in both male and female mammals. Progesterone appears to be a common intermediate in the transformation of cholesterol into both androgenic and estrogenic steroids, as well as adrenocortical hormones. (2) Whereas estrogenic activity is a property of many types of nonsteroidal molecule, very few substances that are not steroids have been found to be androgenic, and those that have are only feebly active. (3) The natural ovarian estrogens, and their more potent non-steroidal synthetic congeners (such as diethylstilbestrol), exert their estrogenic effects in doses which are two to three orders of magnitude lower than those at which testosterone displays its major androgenic actions. ( 4 ) Although there is evidence that estradiol-17B can be concentrated in certain female secondary sexual tissues, and can induce uterine growth without undergoing any chemical change (Jensen, '63), metabolic transformation products of testosterone and A'-androstene-3,17-dione are readily detectable in male accessory sexual organs soon after administration of these steroids in physiological doses (Harding