Testosterone In Adult Rats Research Articles

Does the non-genomic effect of testosterone on social anxiety require the presence of a classical steroid receptor?

Steroid hormones may act through a rapid mechanism that does not require an intracellular steroid receptor and its effects on gene expression. In this study we have analysed this so-called non-genomic effect of testosterone on social anxiety in rats of both sexes using androgen and oestrogen receptor blockers. Male rats were divided into four groups: SHAM-CTRL (a sham operated group treated with oil as vehicle, n=10), SHAM-TST (a sham operated group treated with testosterone at a dose of 1 mg/kg, n=10), GDX-CTRL (a castrated group treated with oil, n=10) and GDX-TST (a castrated group treated with testosterone at a dose of 1 mg/kg, n=10). Female rats were divided into two groups: OVX-CTRL (an ovariectomized group treated with oil, n=10) and OVX-TST (an ovariectomized group treated with testosterone, n=10). The intracellular androgen receptor was blocked with flutamide and both intracellular oestrogen receptors were blocked with tamoxifen (a selective oestrogen receptor modulator). Rats were tested one hour after oil or testosterone administration in the social interaction test. Although the concentration of testosterone was higher in testosterone groups, no significant difference in social interaction was observed between the groups. In summary, in this first study focusing on the non-genomic effects of testosterone on social interaction no rapid effects of testosterone in adult rats were found. Further studies should analyse potential non-genomic effects of testosterone on other forms of social behaviour.

Sertoli cell ectoplasmic specializations in the seminiferous epithelium of the testosterone-suppressed adult rat.

The Sertoli cell ectoplasmic specialization is a unique junctional structure involved in the interaction between elongating spermatids and Sertoli cells. We have previously shown that suppression of testicular testosterone in adult rats by low-dose testosterone and estradiol (TE) treatment causes the premature detachment of step 8 round spermatids from the Sertoli cell. Because these detaching round spermatids would normally associate with the Sertoli cell via the ectoplasmic specialization, we hypothesized that ectoplasmic specializations would be absent in the seminiferous epithelium of TE-treated rats, and the lack of this junction would cause round spermatids to detach. In this study, we investigated Sertoli cell ectoplasmic specializations in normal and TE-treated rat testis using electron microscopy and localization of known ectoplasmic specialization-associated proteins (espin, actin, and vinculin) by immunocytochemistry and confocal microscopy. In TE-treated rats where round spermatid detachment was occurring, ectoplasmic specializations of normal morphology were observed opposite the remaining step 8 spermatids in the epithelium and, importantly, in the adluminal Sertoli cell cytoplasm during and after round spermatid detachment. When higher doses of testosterone were administered to promote the reattachment of all step 8 round spermatids, newly elongating spermatids associated with ectoplasmic specialization proteins within 2 days. We concluded that the Sertoli cell ectoplasmic specialization structure is qualitatively normal in TE-treated rats, and thus the absence of this structure is unlikely to be the cause of round spermatid detachment. We suggest that defects in adhesion molecules between round spermatids and Sertoli cells are likely to be involved in the testosterone-dependent detachment of round spermatids from the seminiferous epithelium.

Vascular Endothelial Growth Factor Is Up-Regulatedin Vitroandin Vivoby Androgens

Evidence from pathophysiological studies support the concept that embryonic development, tumor progression, and hormonally-regulated tissue masses such as adult prostate and corpus luteum are angiogenesis-dependent. We examined if the prostatic expression of vascular endothelial growth factor (VEGF), the major regulator of normal and pathological angiogenesis, was regulated by testosterone. Northern blot of VEGF messenger ribonucleic acid (mRNA) extracted from a human immortalized epithelial prostatic cell line (PNT1) showed that dihydrotestosterone (DHT) up-regulated VEGF mRNA at a level comparable to that observed upon exposure to growth factors. Polymerase chain reaction of reverse transcribed mRNA demonstrated that the ratio of the two splice variants encoding the 121 and 165 isoforms of VEGF were not affected by DHT. VEGF biological activity, measured in the conditioned medium by radio receptor assay, was increased by DHT. Injection of testosterone in adult rats induced a transient increase of the ventral lobe weight and the specific activity of prostatic VEGF, leading to a 7-fold increase in the prostate content of VEGF.

To What Extent Can Spermatogenesis Be Maintained in the Hypophysectomized Adult Rat Testis with Exogenously Administered Testosterone?*

In a previous study it was demonstrated that spermatogenesis can be maintained quantitatively with exogenously administered testosterone in adult intact rats that lack LH. The studies described herein were designed to examine the extent to which spermatogenesis can be maintained quantitatively with exogenously administered testosterone in adult rats that lack all pituitary hormones. Adult male rats were hypophysectomized and testosterone was administered at the time of hypophysectomy via sustained release polydimethylsiloxane (PDS) capsules of increasing lengths. We used the PDS capsules to clamp testosterone at defined concentrations within the seminiferous tubule fluid over a 2- to 3-month treatment period. Mean testis weights and advanced spermatid numbers per testis stabilized by 8 weeks of testosterone treatment regardless of testosterone dose. Both testis weight and advanced spermatid number responded to testosterone dose, reaching plateaus of 1.2 g and 170 x 10(6) per testis, respectively. These values were 60% of, and significantly less than, the respective control values. This result was in striking contrast to the results of our previous study of LH-suppressed intact rats, in which exogenously administered testosterone resulted in testis weights and advanced spermatid numbers that plateaued at values not significantly different from those in controls. These different effects of testosterone in intact and hypophysectomized rats occurred despite the fact that the seminiferous tubule fluid testosterone concentrations achieved in the hypophysectomized rats (up to 25 ng/ml) were greater than the minimal testosterone concentration found previously to be required to maintain spermatogenesis quantitatively in LH-suppressed intact rats (13 ng/ml). Taken together, these results demonstrate clearly that intratesticular testosterone doses that are as high as or higher than those that maintain spermatogenesis quantitatively in intact rats lacking LH fail to maintain spermatogenesis quantitatively in rats lacking all pituitary hormones.

Effect of restraint stress on gonadal proopiomelanocortin peptides and the pituitary-testicular axis in rats

We examined the effect of restraint on testicular interstitial fluid (TIF) concentrations of ACTH, β-endorphin-lipotropin (β-E-LI) and testosterone and correlated those changes with plasma concentrations of ACTH, β-E-LI, corticosterone, LH and testosterone in adult rats. Animals were subjected to 1, 2, or 3 h of restraint and were killed immediately following the stress period. Plasma values of ACTH and β-E-LI were elevated above control values after 1 and 2 h, but not after 3 h of restraint. Plasma corticosterone showed a similar response to restraint except that concentrations were also elevated after 3 h. Plasma testosterone concentrations were elevated after 1 h of restraint, but after 3 h of restraint had fallen below control values. Restraint reduced plasma testosterone concentrations without altering plasma LH concentrations. The decline in plasma testosterone during restraint was associated with a parallel decrease in testosterone in the TIF. Concentrations of ACTH and β-E-LI were 6- and 3-fold greater in TIF than in the plasma. While 1 or 2 h of restraint did not affect ACTH and β-E-LI in TIF, values of these hormones were elevated in rats exposed to 3 h of restraint. These data, coupled with recent reports that testicular proopiomelanocortin (POMC)-derived peptides may modulate testicular steroidogenesis, suggest that these factors may play an autocrine or paracrine role in mediating stressor-induced changes in testicular function.

Changes in the secretion of ABP into testicular interstitial fluid with age and in situations of impaired spermatogenesis.

Androgen-binding protein (ABP) was measured in serum and testicular interstitial fluid (IF) from rats during sexual maturation or in adult rats in which impairment of spermatogenesis had been induced by (i) testosterone withdrawal following Leydig cell destruction, (ii) local heating (43 degrees C) of the testes for 30 min or (iii) induction of unilateral cryptorchidism (UCD). The changes observed were related to the IF levels of testosterone and, in most instances, to the serum levels of FSH. The levels of ABP in serum and IF decreased together with age, being highest at 30 days, falling steeply by 40 days and then slowly but progressively up to 100 days of age. A similar pattern was observed for serum FSH, except that the initial fall occurred beyond 40 days of age. Treatment with EDS or exposure to local heating caused comparable reductions in testicular weight (25-30% by 7 days after treatment, 50% by 21-28 days) and raised the serum levels of FSH. In both groups the levels of ABP in IF were increased by two- to three-fold while the levels of testosterone were either reduced markedly (EDS-treatment) or remained unchanged (local heating). In rats made UCD for 60 days, the weight of the abdominal testis was reduced by 75%, compared with the contralateral scrotal testis, while the IF levels of ABP and testosterone were significantly increased (55%) and decreased (90%), respectively. Short-term (3 days) deprivation of testosterone in adult rats, following immunoneutralization of LH, was without significant effect on IF levels of ABP. It is concluded that ABP secretion into IF is increased in situations of subnormal (or sub-adult) numbers of germ cells and this is usually associated with high levels of FSH. Measurement of ABP levels in IF should prove of value for the monitoring of Sertoli cell function in vivo and may be of diagnostic use for the detection of changes in germ cell numbers.

Study of absorption and retention of nitrogen in fast growing rats--II. Influence of IMAO (nialamide).

A study was made in fast growing rats (65 g) of the nutritive effects of protein and the effect on different organs when influenced by nialamide (IMAO), administered at a dosage of 10 mg/100 g diet, with food intake controlled (pair fed). The administration of nialamide reduces the protein absorbed and retained to a significant degree, both in males and females. No difference was observed between the sexes caused by the effect of the drug, due to the absence of the hormonal anabolizant situation caused by testosterone in adult rats. The administration of nialamide does not significantly modify nitrogen content per 100 g of body weight in any of the organs studied, with the exception of the longissimus dorsi.

Temporal aspects of the dependency of a dimorphic rate of extinction on testosterone

Previous work has shown that rate of extinction of a conditioned taste aversion is affected by concurrent levels of testosterone in adult rats. In the present study, castrated male and female adult rates were given either oil or testosterone during acquisition of the conditioned taste aversion and then either oil or testosterone during extinction. The males and females that received testosterone during the extinction of the aversion showed the slower, masculine rate of extinction regardless of the type of injections they received during acquisition. Conversely, the animals that received oil during extinction showed the faster, feminine rate of extinction regardless of the type of injection during acquisition. In light of these findings, a number of alternative behavioral changes that could account for the effect of testosterone on the rate of extinction were evaluated.