Publisher Summary This chapter describes the hormonal effects on cell proliferation in rat prostate. The growth and function of male accessory sex glands are under the direct control of androgens, and consequently these tissues can potentially serve as an excellent model system for the study of the regulation of cell proliferation by steroid hormones. Three phases can be distinguished in the response of rat prostate to changes in the hormonal status of the animal, and these are summarized. It is found that treatment of castrated rats with testosterone propionate produced a massive but transitory increase in the incorporation of radioactive thymidine into DNA of prostate both in vitro and in vivo, which was paralleled by an elevation and decline in DNA polymerase activity. It is observed that a vital factor determining the magnitude of the proliferative response of prostate to androgens is the number of cells in the gland relative to normal. Tissues that contain fewer than the normal number of cells respond to hormone administration by proliferating rapidly, but once the number of cells has returned to normal the rate of proliferation declines sharply.

Hormonal effects on cell proliferation in rat prostate.

This review is a discussion of recent developments in our understanding of the metabolic changes that occur in skeletal muscle following treatment with glucocorticoid and androgenic steroid hormones. Exposure of muscle to glucocorticoids results in protein wasting due to a reduction in protein synthesis and an increase in intracellular proteolysis. The protease involved in this response appears to be located in the myofibrillar fraction and its activity is increased by glucocorticoid treatment as well as starvation, diabetes, and tumor-induced cachexia. Treatment with androgens causes an anabolic response in skeletal muscle, mainly due to enhancement of protein-synthesizing machinery. These metabolic changes are reviewed in the light of our current knowledge of the functional role of receptor proteins in steroid hormone action. In rat muscle, two classes of receptors are present that bind cortisol and the synthetic steroids dexamethasone and triamcinolone acetonide, respectively. The cortisol-binding macro-molecule resembles cortisol-binding glubulin or transcortin in several of its physicochemical properties. Attempts to identify specific receptors for androgens in rat skeletal muscle have not been successful. However, in this tissue androgens compete, both in vivo and in vitro, with the receptor proteins that bind dexamethasone. Thus the antagonism of glucocorticoid-induced muscle wasting by concomitant androgen administration may be a consequence of the competition between these steroids for the same site on a receptor in muscle which mediates the catabolic action of glucocorticoids. Current progress in the area of muscle response to steroidal hormones depends on the development of procedures for the measurement and identification of proteolytic enzymes in muscles that are involved in the muscle-wasting diseases. A new approach to the study of muscle protein degradation is based on evidence that 3-methylhistidine is a unique amino acid insofar as it is present in skeletal muscle in relatively high concentrations. The methylation of histidine to form this derivative takes place only after histidine is incorporated into protein. Since the methyl derivative is not reutilized for protein synthesis, the rate of release of 3-methylhistidine from muscle serves as a marker for protein degradation. Future studies are also required to assess the role of normal and abnormal concentrations of blood glucocorticoids in muscle metabolism, and to delineate the sequence of events occurring in these target cells following cytoplasmic binding of the hormones and culminating in the catabolic response.

Interaction of glucocorticoids and androgens with skeletal muscle.

Publisher Summary This chapter discusses the molecular action of androgen in the normal and neoplastic prostate. Androgens are steroid hormones that are required for normal male sexual development and maintenance of the male phenotype. Testosterone is the most abundant circulating androgen in males and secreted principally by the Leydig cells of the testis. The adrenal glands produce a small amount of circulating testosterone either directly or by peripheral conversion of secreted androstenedione or dehydroepiandrosterone. The ovary produces a small amount of testosterone in females. 5α-dihydrotestosterone (5α-DHT) is also produced by the testis, but most of the circulating 5α-DHT is derived from the metabolic conversion of testosterone in target tissues and organs. Antiandrogens can be very effective at inhibiting androgen binding and the activation of the androgen receptor (AR), but they can cause undesirable side effects. Inhibitors of 5α-reductase may have advantages over antiandrogens, because they can selectively suppress 5α-DHT-dependent disorders such as prostate cancer, benign prostatic hypertrophy (BPH), acne, baldness. It is found that amino-terminal truncations in rat AR resulted in loss of activity when the steroid-binding domain was present, but the loss was much less severe when the steroid-binding domain was absent also. The presence of the amino-terminal domain also appears to inhibit the rate of steroid dissociation from the receptor and thereby stabilizes the receptor against degradation.

Molecular action of androgen in the normal and neoplastic prostate.

Translational regulation by steroids. Identification of a steroid modulatory element in the 5'-untranslated region of the myelin basic protein messenger RNA.

Glucocorticoid effects on peptide-chain initiation in skeletal muscle and heart

The initiation of protein synthesis by ribosomal particles of rat ventral prostate was studied by measuring ribosomal binding of an initiator (35-S)methionyl-tRNAf. The binding activity is dependent on ribosomes, GTP, and a prostate cytosol protein fraction. The 40S but not the 60S ribosomal subunit particles are active. The cytosol activity decreases rapidly within one hour after the rat is castrated. This loss is prevented by an intraperitoneal injection of 17beta-hydroxy-5-alpha-androstan-3-one (5-alpha-dihydrotestosterone). The cytosol activity can be stimulated almost immediately (within 10 min) after an intravenous injection of low dose (15 mug per rat) of 5-alpha-dihydrotestosterone into the castrated rat.

Shutsung Liao

Papers

A very rapid effect of androgen on initiation of protein synthesis in prostate.