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P. M. Collins and W. N. Tsang

Summary. The ability of testicular steroids to maintain the quantitative aspects of spermatogenesis was compared with reference to their androgenic properties. Hypophysectomized rats were injected daily with 0·2 mg progesterone, 20α-dihydroprogesterone, 3β-hydroxy-5α-pregnan-20-one, testosterone or testosterone propionate for 30 days beginning 2 days after the operation. Testosterone propionate was the most potent steroid tested both in terms of its peripheral androgenic effects and its ability to prevent the post-operative decline in the weight of the testis and seminiferous tubules and the numbers of germ cells throughout their differentiation. The natural androgen, testosterone, exhibited weak gametogenic properties and only partly maintained the normal measures of spermatogenesis. Progesterone exhibited low intrinsic androgenic potency yet was significantly more effective than testosterone in maintaining spermatogenesis; it prevented the degeneration of spermatocytes during the later stages of meiotic prophase and the reduction divisions resulting in an increased yield of step 7 spermatids. Low androgenic and gametogenic properties were exhibited by 20α-dihydroprogesterone and 3β-hydroxy-5α-pregnan-20-one. These results may indicate that testosterone produced locally in the seminiferous tubules from progesterone is more effective in maintaining spermatogenesis than androgens entering from the circulation. Alternatively, progesterone may act more directly on the germ cells than previously envisaged.

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Androgens are capable of maintaining the progressive development of the germ cells in immature male rats which have either been hypophysectomized (Leathem, 1944; Ludwig, 1950; Lostroh, 1969) or treated with compounds which interfere with the release and/or secretion of gonadotrophins (Ludwig, 1950; Kalra & Prasad, 1967; Steinberger & Steinberger, 1969). Similar results have also been obtained in adult male rats (Boccabella, 1963; Clermont & Harvey, 1967; Lacy & his co-authors, 1969). Studies on steroid metabolism in vitro by isolated seminiferous tubules of rats denuded of their germ cells by heat-treatment has led to the view that not only Leydig cells but also Sertoli cells may be a major source of androgens (Collins, Bell & Vinson, 1968; Lacy et al., 1969). Similar conclusions have also been reached by Ellis & van Kampen (1971) from studies on

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Several workers have studied various parameters as an index of Leydig cell differentiation and attempted to correlate them with the growth of the accessory sex organs. In the prepuberal rat, little correlation seems to have been achieved (see Niemi & Ikonen, 1963; Clegg, 1966). Others have examined testosterone production in vitro by the immature testis and attempted to correlate this with the increase in weight of the seminal vesicles and prostate gland. In this connection, a good deal of attention has been paid to the production of testosterone in vitro and its apparent regulation by 5α-reductase activity. Nayfeh, Barefoot & Baggett (1966) reported an increase in testosterone production per unit weight of tissue at about the time of sexual maturity and suggested that this might be due mainly to reduced metabolism to 5α-androstane-3α,17β-diol (androstanediol). Inano, Hori & Tamaoki (1967) found a remarkable increase in the activity of various enzymes

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P. M. Collins, W. P. Collins, A. S. McNeilly and W. N. Tsang

Summary. Rats were treated by exposure of the scrotum to a temperature of 43°C for 30 min or bilateral ligation of the vasa efferentia and bled at 0, 3, 7, 14 and 21 days after treatment. In heat-treated rats FSH levels rose linearly from pretreatment levels while those in efferentiectomized animals remained unchanged for 3 days before increasing. In both groups FSH concentrations reached similar maximum values after 7 days and were significantly higher than those of intact controls at 7, 14 and 21 days. LH levels, although not generally different from those in the controls, rose from pretreatment levels in parallel with FSH. No differences were found in testosterone concentrations in any of the groups. Histological examination at 3 weeks after treatment confirmed that the germinal epithelium consisted mainly of spermatogonia and Sertoli cells. The cytological appearance and lipid content of the Leydig cells of the aspermatogenic testes were indistinguishable from those of the controls and the weight and histological appearance of the accessory sex organs and the fructose content of the coagulating glands were also normal. It is concluded that the sterilizing effects of heat treatment and efferentiectomy are independent of changes in Leydig cell function and that the increase in gonadotrophin levels is related to the germ cell degeneration.