Pituitary LH and FSH and testosterone secretion in infants with undescended testes.

Twelve male infants with undescended testes (5 bilaterally, 7 unilaterally) were studied between the ages of 1 week and 11 months. As in older pre-pubertal cryptorchid boys, a significant decrease of the LH response to LH-RH test was found, while basal plasma levels of gonadotrophins and FSH response to LH-RH were normal. Plasma testosterone levels were in the normal range, and Leydig cells responded to stimulation by HCG, the degree of this response being significantly and positively correlated to the LH peak elicited by LH-RH. It may be concluded that some early defect of the pituitary-Leydig cell axis is associated with undescended testis.     

Gonadotropin specificity of in vitro testosterone secretion by fish testes

Highly purified gonadotropin preparations from representatives of all four tetrapod classes and several fish were used to examine the specificity of in vitro testosterone production by minced testes from four species of teleost fish, representing three families and two orders. No consistent phylogenetic patterns emerged in either hormonal ($\text{FSH}\text{LH}$) or phylogenetic specificity in the steroidogenic response of the teleost testis. Testes of Gillichthys mirabilis (Family Gobiidae) were highly specific for all species of LH (FSHs were inactive) and they also showed a certain degree of species specificity; mammalian and amphibian LHs were much more potent than reptilian and avian LHs. In contrast, testes of Cichlasoma citrinellum and Sarotherodon mossambicus (Family Cichlidae) lacked gonadotropin specificity (most preparations of FSH and LH were about equipotent), and in C. citrinellum all species of tetrapod hormones were active within approximately the same dose range. Gonadotropins from the sturgeon (Chondrostei) were the most potent in both G. mirabilis and C. citrinellum. In Salmo gairdneri (Family Salmonidae) there was specificity for amphibian (bullforg) LH, but not for mammalian (ovine) LH. Steroid secretion by the fish testes was temperature dependent, but relative potencies of ovine LH, bullfrog LH, and sturgeon gonadotropin were not altered by incubation temperatures between 10 and 30° in G. mirabilis. As a group, the teleosts examined here differ from mammals, birds, and reptiles in their hormonal specificity (or consistent lack there of) for testicular androgen secretion; they most closely resemble the Amphibia in their high degree of interspecific variability in response to FSH and LH. The lack of predictability in this aspect of specificity as well as in species specificity in the potencies of individual types of hormones of different origins precludes generalizations about the evolutionary pattern of gonadotropin-testis interactions.     

Changes in the testosterone to dihydrotestosterone ratio in plasma and testes of maturing rabbits.

Testosterone (T) and dihydrostestosterone (DHT) were radioimmunologically assayed in the testes and plasma of rabbits at 1, 10, 20, 40, and 60 days of age and at 3, 4, 5, and 8 months. In the testis (nanograms per 100 mg testis) and plasma (picograms per ml), both hormones are low at birth, reach their maxima between 60--90 days, and then decline and remain low after 120 days. In the testes, the T:DHT ratio is very high from birth (4.2 +/- 0.4) to 60 days (8.8 +/- 1.1). A significant decrease (P less than 0.001) occurs between 60 (8.8 +/- 1.1) and 90 (1.2 +/- 0.1) days. The T:DHT ratio is always less than or equal to unity after 90 days. From 1--60 days, T is the dominant testicular hormone, while the levels of DHT are greater than or equal to those of T after 60 days. The mean value of the plasma T:DHT ratio is always greater than unity from birth (1.7 +/- 0.4) to adulthood (2.6 +/- 0.7). The dominant circulating hormone, at all ages, is T. Our results show that sexual maturation in rabbits is characterized by an inversion of the T:DHT ratio in the testes but not in the plasma.     

Characterization of a nuclear receptor for testosterone in seminiferous tubules of mature rat testes.

A specific androgen receptor could be demonstrated in the nuclear and cytoplasmic fractions of testicular tissue of mature hypophysectomized rats, either in vivo after injection of testosterone or in vitro after incubation of testis tissue with testosterone. Using agar-gel electrophoresis this receptor could be distinguished from the testicular transport-like protein for androgens (androgen binding protein = ABP). After in vivo administration of testosterone the steroid bound to the receptor in mature rat testis was mainly unmetabolized testosterone. After dissection of testis tissue the larger part of the receptor was shown to be present in the seminiferous tubules. The amount of exogenous testosterone that could be bound per mg of protein in the nuclear extract increased gradually during 20 days after hypophysectomy. Some characteristics of the receptor in the nuclear extract and of ABP were compared : the receptor was more sensitive to temperature increases than ABP; the steroid dissociated more slowly from the receptor than from ABP; cyproterone acetate showed almost no effect on the binding of dihydrotestosterone to ABP, but did compete for the receptor binding sites in the nuclear extract.     

Short-term stress increases testosterone secretion from testes in male domestic fowl

Prolonged stress inhibits the hypothalamus-pituitary-gonadal (HPG) axis and reduces plasma testosterone (T). However, enhanced secretion of luteinizing hormone (LH) and T has been documented during the initial stages of acute stress in mammals. This study assayed the effect of short-term stress on plasma T and corticosterone (B) in juvenile, pubertal, and adult White Leghorn cockerels. Stress was induced by brief physical restraint of caged juvenile (7 weeks), pubertal (17 weeks), and adult (40 weeks) cockerels, as well as 40-week-old adults reared together in a room lined with wood shavings (group reared). Blood was sampled immediately before restraint (0 time), at the end of a 10-min restraint period, and at 30, 60, and 180 min after 0 time. Restraint resulted in an initial increase in plasma T in all groups, along with a rise in B. Whereas B generally reached its peak level at the end of the restraining period, T peaked 20 min later. The maximum increase of T and B relative to prestress levels (T and B ratios) was similar in all groups, with median T ratio reaching 1.25-1. 5-about half that of the B ratio. Thus, the extent of T and B response to short-term stress was not influenced by basal levels of T, which were highest in adults, and basal levels of B, which were higher in caged adults than in group-reared adults. Injection of ACTH did not induce a greater increase in plasma T than in sham-injected controls. Further, the elevation of T in response to stress was extinguished in castrated adults, indicating that T is secreted from the testes rather than the adrenals in response to stress. When the same regime of blood sampling was applied to adults not subjected to restraint, the T ratio rose by up to 11 times. It can therefore be stipulated that T response depends on the type of stress applied, a factor that should be considered when investigating androgen levels in plasma.     

Ketoconazole blocks testosterone synthesis

Ketoconazole, a new oral drug used to treat systemic and superficial mycoses, inhibits sterol synthesis in fungi. The development of gynecomastia in two patients prompted us to investigate the effect of the drug on testosterone production. After a 200-, 400-, or 600-mg dose, volunteer male testosterone serum concentrations fell markedly, but returned toward baseline eight to 24 hours later as ketoconazole serum concentrations waned. A marked but transient drop in testosterone levels occurred in patients receiving long-term therapy, and continuous testosterone depression was noted in one. A block of synthesis was demonstrated in vitro. Ketoconazole at concentrations achievable in serum with currently used doses blocked basal and gonadotropin-stimulated testosterone production by rat Leydig cells. The diminution of testosterone synthesis could be significant as further therapeutic trials may use larger doses or more than once-daily administration. The paucity of reports of endocrinologic toxicity may relate to the "escape" from the block demonstrated in vivo.     

Cimetidine blocks testosterone synthesis

Although an assortment of endocrine dysfunctions are reported in men treated with cimetidine hydrochloride, gonadotropin and sex steroid levels are usually normal. A 66-year-old man with previously normal sexual function presented with breast tenderness and sexual dysfunction after receiving cimetidine. His plasma testosterone level was low, and elevated gonadotropin levels suggested a primary testicular disorder. His sexual dysfunction improved and his plasma testosterone level rose to normal after cimetidine therapy was discontinued. Readministration of cimetidine therapy resulted in the prompt recurrence of his sexual problems and low testosterone level. A reversible defect in 17-beta-hydroxysteroid dehydrogenase is the mechanism postulated to have caused his low testosterone level. While the frequency of this abnormality is uncertain, its reversible nature and the wide use of cimetidine make it an important cause of sexual dysfunction in men.