Ultrastructural changes in the principal & clear cells in the rat epididymis following the administration of cyproterone acetate.
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Biomedical subjects
Publications and source records attributed to M Rajalakshmi.
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The in vitro metabolism of [3H] testosterone (17beta-hydroxy-4-androsten-3-one), [3H] androstenedione (4-androstene-3,17-dione) and [3H] dehydroepiandrosterone (3beta-hydroxy-5-androsten-17-one) by cauda epididymal spermatozoa from the rat, rabbit, hamster, guinea-pig and ram, varied between species. There were differences in the androgens utilized, the extent of their conversion and the identities of the metabolites formed. Of the steroid substrates tested rat spermatozoa metabolized testosterone preferentially while spermatozoa from guinea-pig transformed [3H] dehydroepiandrosterone (DHEA) almost exclusively. Rabbit spermatozoa converted all three [3H] androgens while hamster sperm utilized [3H] testosterone and [3H] DHEA. Spermatozoa collected from rams killed at the abattoir metabolized both [3H] androstenedione and [3H] DHEA but this capacity was dramatically reduced in spermatozoa collected from rams subjected to short-term anaesthesea. The results are discussed in relation to the possible direct roles of androgens in sperm physiology.
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The metabolism of 3H-testosterone by the epididymis and accessory organs of adult male rats exposed continuously to microdoses of cyproterone acetate from subcutaneous capsules were studied. The major metabolite of 3H-testosterone in the epididymis, vas deferens and ventral prostate of control rat was dihydrotestosterone while the formation of androstanediol by these tissues was low. The highest percentage of DHT was formed by the ventral prostate and cauda epididymis. In rats exposed to cyproterone acetate for four months, the conversion of testosterone to DHT was inhibited in all the tissues but maximally in the ventral prostate and cauda epididymis. In these rats, the secretory function of the ventral prostate was normal while that of the epididymis was markedly decreased. These data are discussed based on the differential thresholds of androgens required to regulate the functions of the accessory organs.
The effects of a single dose to testosterone on the content of DNA, RNA and protein and the incorporation of [3H]phenylalanine into protein in the epididymis, vas deferens and ventral prostate of the rat were studied. A single dose of testosterone did not increase the weights of the accessory organs but restored the incorporation of [3H]phenylalanine into proteins in the catput, corpus and cauda epididymides, vas deferens and ventral prostate to the normal level. Within 1 h of hormone administration, significant increases in the content of DNA, RNA and protein were noticed in the cauda epididymidis and ventral prostate. The catput and corpus epididymides and was deferens whoed decreasing order to responsiveness to testosterone. These data are discussed with respect to the relative responsiveness of these organs to reinitiation to their function by administration of a single dose of testosterone. The new protein(s) synthesized in response to hormonal stimulation associated with growth and secretory activity of the cells may be different from the new protein macromolecules synthesized after hormone withdrawal or inhibition of hormone action which are involved in autolytic processes.
The present status and perspectives in the control of fertility in the male have been reviewed. There are two potential sites in the male reproductive processes that can be used as targets for regulation of fertility in the male: (1) inhibition of spermatogenesis, and (2) interference with sperm maturation in the epididymis. A variety of compounds tested for their antispermatogenic action in laboratory animals have no future for the control of fertility in the human male because of a number of undesirable side effects (cf. Prasad, 1973). Progestational compounds inhibit spermatogenesis by affecting the hypothalamo-hypophysial system and result in impairment of libido. The possibility of adjustment of the minimal dose of progestational compounds required to induce suppression of spermatogenesis and reduction of plasma testosterone to a level compatible with the maintenance of normalcy of libido and potency needs to be studied. A new approach to contraception in the male involves the use of a combination of progestational compounds for suppression of spermatogenesis along with testosterone (administered through silastic capsule implants or as intramuscular injections) for maintenance of libido and accessory sex gland function. A number of such combinations have been tested clinically with some success. However, the limitations of side effects, such as weight gain, gynecomastia, and psychological complications preclude their long-term use for contraception in man. Short-term use of these combination regimens by the male for 1 year followed by use of a contraceptive method by the female may be desirable to encourage partnership in family planning. Although testosterone and other androgens suppress spermatogenesis in man, the feasibility of their use for contraception depends on the establishment of a dosage and mode of adminstration that provide antispermatogenic action without causing more general metabolic alterations. Inhibition of spermatogenesis by selective interference with the action of FSH on the Sertoli cells by active or passive immunization or by selective suppression of synthesis and release of FSH by administration of "Inhibin" offers exciting possibilities in the control of fertility in the male. Studies on the physiology of the rete testis highlight its importance as a post-tubular site of action of antifertility agents in conveying (to the epididymis) compounds interfering with epididymal functions and/or viability of spermatozoa. A new approach to the induction of functional sterility in the male by selective alteration of epididymal function by a local androgen deprivation effect has been successfully tested in clinical trials. Small doses of cyproterone acetate, administered orally, result in maintenance of libido and accessory sex gland function accompanied by a decrease in the motility of ejaculated spermatozoa and incomplete inhibition of spermatogenesis...
The factors regulating the physiology of the epididymis and the induction of functional sterility by alteration of epididymal function are discussed. The threshold requirement of androgens to maintain the structural and functional integrity of the epididymis in the rat, hamster and monkey is much higher than that needed by the accessory glands. Further, the cauda epididymidis has a higher threshold requirement of androgens than the caput epididymidis and may reflect the differences in the availability and metabolism of androgens to these two segments. An inverse relationship exists between the levels of sialic acid (sialoproteins) in the epididymal luminal plasma and that bound to the spermatozoa in the cauda epididymidis. Androgen deprivation and consequent alteration of the secretory activity of the epididymis either by castration or by treatment with antiserum to LH or by the antiandrogen, cyproterone acetate, caused concurrent decrease in the levels of sialic acid in the luminal plasma and in the spermatozoa of the different regions of the epididymis. These changing patterns of sialic acid in the spermatozoa and luminal plasma may be associated with changes in the surface charge of the spermatozoa and the stabilization of the acrosome and its membranes during sperm maturation.
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The effects of cyproterone acetate on the accessory organs of immature, prepubertal, and sexually mature adult rats were studied. Administration of CA to immature 30-day-old rats for 15 days markedly decreased the silaic acid in the caput and cauda epididymides and decreased the secretory activity of the accessory glands. Treatment of adult rats with CA for 15 days caused an increased incorporation of 3H-uridine into RNA and of 3H-phenylalanine into protein in the caput and cauda epididymides. The percentage of increase in the specific activity of RNA and protein was higher in the cauda epididymidis than in the caput epididymidis.
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