Forskolin ameliorates mancozeb‐induced testicular and epididymal toxicity in Wistar rats by reducing oxidative toxicity and by stimulating steroidogenesis

In the present study, we have tested the beneficial effects of forskolin in protecting the mancozeb‐induced reproductive toxicity in rats. Adult male Wistar rats were exposed to either mancozeb (500 mg/kg body weight/day) or forskolin (5 mg/kg body weight/day) or both for 65 days and analyzed for spermatogenesis and steroidogenesis and testicular and epididymal oxidative toxicity. A significant decrease in daily sperm production, epididymal sperm count, motile, viable, and hypo‐osmotic swelling‐tail swelled sperm was observed in mancozeb‐treated rats. The activity levels of testicular 3β‐hydroxysteroid dehydrogenase and 17β‐hydroxysteroid dehydrogenase and circulatory testosterone levels were significantly decreased in mancozeb‐treated rats. Exposure to mancozeb resulted in a significant decrease in glutathione levels and superoxide dismutase and catalase activity levels with an increase in lipid peroxidation levels in the testes and epididymis. Coadministration of forskolin mitigated the mancozeb‐induced oxidative toxicity and suppressed steroidogenesis and spermatogenesis.     

Long-term chemical castration induces depressive symptoms by suppressing serotonin expression in rats

Androgen deprivation therapy, also known as chemical castration, has been used as an adjunct to psychotherapy for sex offenders. Goserelin and bicalutamide are drugs used for chemical castration. Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter involved in mood changes, such as depression. We investigated the effects of surgical and chemical castration on depressive symptoms in rats. Surgical castration was performed through a bilateral orchiectomy. Bicalutamide was administrated orally once a day for 84 consecutive days. Goserelin acetate was implanted subcutaneously into the anterior abdominal wall, and this implantation was repeated 3 times at 28-day intervals. Testosterone levels were detected by enzyme-linked immunosorbent assays. Sexual behaviors were analyzed by measuring mount latency, mount frequency, intromission latency, and intromission frequency. The forced swimming test was performed to evaluate rats’ depression status. To detect 5-HT and tryptophan hydroxylase (TPH)-positive cells in the dorsal raphe, immunohistochemistry for 5-HT and TPH and western blotting for 5-HT1A receptors and TPH were performed. Surgical castration and goserelin decreased testosterone levels and suppressed sexual behaviors. However, bicalutamide did not inhibit sexual behaviors, although it reduced testosterone levels to a limited extent. Both surgical and chemical castration induced depression in rats. The expression of 5-HT, TPH, and 5-HT1A receptors in the dorsal raphe was significantly decreased by both surgical castration and chemical castration via bicalutamide and goserelin. The present results showed that surgical and chemical castration for 12 weeks induced a depressive state in rats by inhibiting serotonergic function through 5-HT1A receptors.     

In vitro effects of Celiptium and MR 14504 on mature rat Leydig cell testosterone production

Percoll-purified mature rat Leydig cells have been used to evaluate the testicular toxicity of two highly potent intercalating agents (Celiptium and MR 14505). Testosterone secretion in the absence and in the presence of human chorionic gonadotropin (hCG) was measured to assess Leydig cell function. Celiptium and MR 14504 induce time- and dose-related inhibitory effects on the production of testosterone by Leydig cells, both in the presence and in the absence of hCG, whatever the concentration of hCG used. We have observed that MR 14504 is about 5 times more potent as an inhibitor of rat Leydig cell steroidogenesis than Celiptium without inducing any cell toxicity. The present study indicates that the Leydig cell is an additional potential site for the primary toxic effects of these drugs in the adult rat testis.     

Plasma concentrations of sex steroids and fighting in male Tilapia zillii

In laboratory-held Tilapia zillii the gonadosomatic index ( I _G) is an accurate predictor of dominance in pairwise fights between males. Immediately after fighting no differences were detected between winners, losers or controls, in plasma concentrations of testosterone (T) or 11-ketotestosterone (11KT). 11KT was correlated negatively with I _G and positively with T. 11KT appeared to be the major androgen in this species, but there was no evidence that simple differences in levels of these sex steroids mediated aggressive behaviour.     

Thermal influences on temporal changes in plasma testosterone and oestradiol-17β concentrations during gonadal recrudescence in female common wolffish

Temperature treatment during ovarian recrudescence influenced temporal changes in plasma testosterone (T) and oestradiol-17β (E₂). In fish exposed to 8 and 12° C early in the cycle the peaks of both T and E₂ were delayed by 4 weeks in comparison with those of fish held at 4° C throughout the experiment. These differences were accompanied by corresponding shifts in the timing of ovulation.     

Seasonal changes in androgen levels in stream- and hatchery-reared Atlantic salmon parr and their relationship to smolting

In stream-reared Atlantic salmon Salmo salar , plasma androgens were significantly greater in mature male parr than immature males and females in October, but had declined by January and did not differ significantly from immature fish throughout the spring. Immature fish in March were significantly larger and had greater gill Na⁺, K⁺-ATPase activity than their previously mature counterparts. Bimodal growth distribution was seen in hatchery-reared Atlantic salmon and a proportion of the male fish in the lower mode matured. Plasma testosterone (T) and 11-ketotestosterone (11-KT) were significantly elevated from September to December in mature male (1+ year) parr. In January, plasma androgens had declined in mature males and did not differ significantly from immature fish. By May all the hatchery fish were large enough to smolt and a proportion of the previously mature males had increased gill Na⁺, K⁺-ATPase activity. Therefore elevated androgens in the previous autumn do not prevent smolting. Parr with higher plasma T and 11-KT in April and May, that are presumably beginning to mature, had lower gill Na⁺, K⁺-ATPase activity, indicating that future maturation and associated increases in androgens may inhibit smolting.     

Conversion of 4-androstene-3,17-dione to testosterone by Pisum sativum

4-Androstene-3,17-dione-[4-¹⁴C] was applied to the leaves of growing pea plants, Pisum sativum. Within a week, 28% of the administered steroid was specifically reduced to testosterone. Part of the testosterone was present in esterified form, and 5α-androstane-3β,17β-diol was also identified as a metabolite, but neither epitestosterone nor estrogens were detected.     

Biotransformation of testosterone and other androgens by suspension cultures of Nicotiana tabacum “Bright yellow”

It has been shown that the cultured cells of Nicotiana tabacum “Bright Yellow” are capable of transforming testosterone to Δ⁴-androstene-3, 17-dione, 5α-androstan-17β-ol-3-one, 5α-androstane-3β, 17β-diol, its dipalmitate and 3- and 17-monoglucosides, epiandrosterone, its palmitate and glucoside, testosterone glucoside. 5α-Androstane-3β, 17β-diol dipalmitate and 3- and 17-monoglucosides, epiandrosterone palmitate and glucoside, and testosterone glucoside have been found for the first time as metabolites of testosterone in plant systems. Δ⁴-Androstene-3,17-dione was converted to testosterone. 5α-Androstan-17β-ol-3-one, which has been recognized as an active form of testosterone in mammals, was also detected. It has also been demonstrated that [4-¹⁴C]testosterone is actively incorporated in these transformations.     

Modifications des cellules gonadotropes de la préhypophyse chez la ratte injectée de testostérone au cours du cycle oestral

Summary 4-day cyclic adult female Wistar rats were injected subcutaneously with testosterone propionate on diestrus 1 at 16:00 and on diestrus 2 at 10:00 respectively. Non-injected females served as controls. Autopsy was performed on diestrus 2 at 23:00, and on proestrus at 14:00 and 17:00 respectively. The blue Alcian-PAS staining was used to evidence FSH () and LH () pituitary cells.In control animals and in diestrus 2 injected females only a small number of FSH cells could be detected on diestrus 2 at 23:00. This number increased markedly on proestrus at 14:00 and decreased on proestrus at 17:00. A similar evolution was observed in diestrus 1 testosterone injected females, but the number of FSH cells appeared higher at any stage of autopsy in these females than in diestrus 2 injected females and in control rats.In control females, numerous LH cells were observed on diestrus 2 at 23:00. The number of these cells was diminished on proestrus at 14:00 and still more at 17:00. On the contrary few LH cells were detected in testosterone injected females on the evening of diestrus 2. An increase of these cells occurred on proestrus at 14:00, followed at 17:00 by only a weak diminution as established by comparison with control animals.An inhibition of FSH release and a suppression of the proestrus surge of LH were therefore supposed to cause, on one hand, the slowing up of follicular growth observed in diestrus 1 injected females and, on the other hand, the blockage of ovulation noted in both diestrus 1 and diestrus 2 treated animals.

Travail effectué avec l'aide de la D.G.R.S.T. Contrat n^o 72.7.0030.     

Androgen-activating enzymes in the central nervous systemProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

In the rat brain, several steroids can be converted by specific enzymes to either more potent compounds or to derivatives showing new biological effects. One of the most studied enzyme is the 5-reductase (5-R), which acts on 3keto-Δ4 steroids. In males, testosterone is the main substrate and gives rise to the most potent natural androgen dihydrotestosterone. In females, progesterone is reduced to dihydroprogesterone, a precursor of allopregnanolone, a natural anxiolytic/anesthetic steroid. Other substrates are some gluco- and minero-corticoids. Two isoforms of the 5-R, with limited degree of homology, have been cloned: 5-R type 1 and type 2. The 5-R type 1 possesses low affinity for the various substrates and is widely distributed in the body, with the highest levels in the liver; in the brain, this isoform is expressed throughout life and does not appear to be controlled by androgens. 5-R type 1 in the rat brain is mainly concentrated in myelin membranes, where it might be involved in the catabolism of potentially neurotoxic steroids. The 5-R type 2 shows high affinity for the various substrates, a peculiar pH optimum at acidic values and is localized in androgen-dependent structures. In the rat brain, the type 2 isoform is expressed at high levels only in the perinatal period and is controlled by androgens, at least in males. In adulthood, the type 2 gene appears to be specifically expressed in localised brain regions, like the hypothalamus and the hippocampus.

The 5-R type 2 is present in the GT1 cells, a model of LHRH-secreting neurons. These cells also contain the androgen receptor, which is probably involved in the central negative feedback effect exerted by androgens on the hypothalamic–pituitary–gonadal axis. The physiological significance of these and additional data will be discussed.