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In the rhesus monkey (Macaca mulatta), the negative feedback regulation of follicle-stimulating hormone secretion by an action of testicular hormone directly at the level of the anterior pituitary gland cannot be accounted for by either testosterone or estradiol.

In the male rhesus monkey, the negative feedback regulation of gonadotropin secretion by the gonad appears to involve a specific inhibitory action of testicular hormone on FSH release at the level of the anterior pituitary gland. The purpose of the present study, which used the hypophysiotropic clamp preparation, was to determine whether circulating testosterone (T) or estradiol (E) comprises a major component of the testicular FSH-inhibiting factor in this species. Endogenous hypothalamic GnRH secretion was abolished or severely compromised in five adult male rhesus monkeys by placement of radiofrequency lesions in the region of the arcuate nucleus. Subsequently, an episodic pattern of activity in the pituitary-Leydig cell axis of these animals was restored by a chronic and unchanging intermittent iv infusion of GnRH (0.1 microgram/min for 3 min ever 3 h), which appears to provide the gonadotropes of lesioned animals with a hypophysiotropic drive comparable to that produced by the hypothalamus of animals with an intact central nervous system. Treatment of three animals with a specific anti-E-gamma-globulin fraction resulted in a marked and sustained rise in E-binding activity in serum, but this neutralization of circulating E did not elicit hypersecretion of FSH. In all five animals, initiation of T replacement on the day of orchidectomy, which maintained circulating T concentrations in the high testis-intact control range, failed to prevent the postcastration hypersecretion of FSH that is evoked after removal of testis in the hypophysiotropic clamp preparation. As expected, the changes in circulating LH levels during immunoneutralization and after orchidectomy and T replacement were unremarkable. These findings indicate that neither circulating T nor E can account for the testicular inhibition of FSH secretion in the rhesus monkey and thus lead, by a process of exclusion, to the view that in this species the negative feedback regulation of FSH release by the testis is mediated directly at the level of the gonadotrope by an inhibitory action of a nonsteroidal hormone, most probably the recently identified gonadal peptide inhibin.

Animals↗

Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus.

Alterations in the circadian time structure of the secretion of several hormones were investigated in 13 male patients infected with human immunodeficiency virus (HIV). Seven were asymptomatic (classified CDC II, according to the criteria of the Atlanta Centers for Disease Control), and 6 had acquired immunodeficiency syndrome (CDC IV). Ten healthy males volunteered as controls. Plasma levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), cortisol, testosterone, ACTH, and beta-endorphin were determined by RIA in blood samples obtained every 4 h from 0830-0830 h the next morning. Data were analyzed both by two-way analysis of variance and the cosinor method. Circadian rhythms were statistically validated for each of the six hormones in each of the three groups of subjects. Compared with the control subjects, mesors (24-h adjusted means) were significantly higher for cortisol and lower for DHEA, DHEA-S, and ACTH (P less than 0.001 for all four hormones) in all HIV-infected patients. Plasma testosterone mesors were similar in controls and CDC II patients, but decreased significantly in the CDC IV patient group (P less than 0.05). Analysis of the circadian rhythms of plasma hormone levels clearly indicated an altered adrenal hormonal state in HIV-infected male patients, even during the asymptomatic period of the infection. For instance, plasma cortisol at 0430 h was more than twice as high in HIV-infected patients as it was in time-qualified controls. Although patients already had elevated plasma cortisol and lowered adrenal androgen levels at this stage, hypogonadism was not observed, as gauged by plasma testosterone concentrations. We speculate that the primary hormonal defect in HIV-infected patients is increased cortisol secretion resulting from circadian-varying stimulation of the adrenal cortex by a factor other than pituitary ACTH. This factor might be a stimulating substance secreted primarily by infected immune cells. Excess cortisol would lower adrenal androgen secretion by shifting adrenal steroid biosynthesis toward glucocorticoids and decreasing pituitary ACTH secretion via a negative feedback mechanism.

Acquired Immunodeficiency Syndrome↗

Testicular hormones reduce individual differences in the aggressive behavior of male mice: a theory of hormone action.

A chronology of theoretical development in studies of the role of testicular hormones in murine aggression is presented. Evidence which brings into question the generality of current theory is reviewed, and the implications of this evidence for the direction of future research are discussed. A new method by which to characterize individual differences in aggressive behavior is described, and recent data which provide the basis for the development of a new theory are presented. It is theorized that testicular hormones reduce individual differences in the aggressive behavior of male mice, and that this behavioral "homogenization" is mediated by a testicular-hormone regulated "discrimination mechanism," possibly localized within the mouse olfactory system. The generality of this theory and the implications for other hormone/behavior systems are also discussed.

Aggression↗

The effect of alkylating agents on the reproductive and hormonal testicular function in patients with rheumatoid arthritis.

An evaluation of testicular function was undertaken in 11 boys and young men aged 14-26 years suffering from rheumatoid arthritis complicated by amyloidosis and treated with cyclophosphamide and chlorambucil. 7 cases were studied during life and 4 at autopsy. Semen analysis showed azoospermia in 4 cases; in one, cryptozoospermia; in one, oligoasthenotheratozoospermia; and in one, asthenoteratozoospermia. In 4 patients with azoospermia and in one with cryptozoospermia, testicular biopsy was done for histo-pathological examination. In patients with azoospermia, only Sertoli cells were present in the seminiferous tubules. In one patient with cryptozoospermia, normal spermato- and spermiogenesis was found only in occasional seminiferous tubules. Microscopic examination of the testis failed to show any changes in the structure of the interstitial gland in any of the patients. Amyloid deposits were found in the vascular walls of the interstitial gland in one patient only. The serum testosterone level was depressed in 3 patients of the 9 examined. The LH level was elevated in 2 patients. The mean value of testosterone-LH ratio was significantly lower in patients treated with alkylating agents as compared with patients not so treated. Serum FSH level was elevated in 6 patients. Post-mortem examination of the testis in 4 patients showed complete absence of the germinal epithelium and only the presence of Sertoli cells. In 2 cases, amyloid deposits were found in the vascular walls in the rete testis. It was concluded that alkylating agents, besides damaging the testicular germinal epithelium, also affect the function of Leydig cells.

Adolescent↗

Effects of neonatal testicular hormones on preference behaviour in the rat.

The effects of neonatal testicular hormones on preference behaviour for an oestrous female rat were investigated. A residential maze was used in which the position of the animals was registered continuously without disturbing them. Two experiments are described. In the first experiment adult male rats which had been castrated within 24 h of birth were given testosterone (T), dihydrotestosterone (DHT) or oestradiol (E2) in a subcutaneous silastic implant. The T- and E2-treated males showed preference for an oestrous female rat over an anoestrous female. The DHT-treated animals showed no interest in a female conspecific, irrespective of her hormonal state. In the second experiment females spayed in adulthood were given a T-containing silastic implant. They showed preference for the oestrous female, like intact males. Removal of the T-implant caused this preference to disappear, while locomotor activity was not affected. It is concluded that neonatal testicular hormones have little effect on adult sociosexual preference behaviour.

Animals↗

Testicular hormone exposure during adolescence organizes flank-marking behavior and vasopressin receptor binding in the lateral septum.

Adolescence is a period during which many social behaviors emerge. One such behavior, flank marking, is a testosterone-modulated scent marking behavior that communicates dominance status between adult male Syrian hamsters. Testosterone modulates flank-marking behavior by altering neural transmission of vasopressin within a forebrain circuit. This study tested whether testicular hormones secreted during adolescence play purely a transient activational role in the display of flank-marking behavior, or whether adolescent steroid hormone secretions also cause long-term organizational changes in vasopressin binding within brain regions underlying flank-marking behavior. We tested this hypothesis by manipulating whether testicular secretions were present during adolescent development and then tested for flank-marking behavior and vasopressin receptor binding within the flank-marking neural circuit in young adulthood. Specifically, males were gonadectomized immediately before or after adolescence, replaced with testosterone 6 weeks following gonadectomy in young adulthood, and behavior tested 1 week later. Adult testosterone treatment activated flank-marking behavior only in males that were exposed to testicular hormones during adolescence. In addition, males exposed to testicular hormones during adolescence exhibited significantly less vasopressin receptor binding within the lateral septum than males deprived of adolescent hormones, suggesting that hormone-dependent remodeling of synapses normally occurs in the lateral septum during adolescence. These data highlight the importance of gonadal steroid hormone exposure during adolescence for the organization of neural circuits and social behavior.

Age Factors↗

Adrenal, thyroid, and testicular hormone rhythms in male golden hamsters on long and short days.

Plasma concentrations of adrenal, thyroid, and testicular hormones were measured at 4-h intervals around the clock in male hamsters on long (14:10-h light-dark cycle) and short (10:14-h light-dark cycle) days. Plasma corticosterone, cortisol, thyroxine (T4), triiodothyronine (T3), and testosterone rhythms were present on long days. The only one of these hormones to have a significant rhythm on short days was cortisol, but even its amplitude was suppressed compared with the cortisol rhythm on long days. Short days also lowered mean plasma levels of cortisol, T4, T3, and testosterone. Finally, short days raised the ratio of corticosterone to cortisol and lowered the ratio of T4 to T3. Both ratios had significant rhythms on long days but not on short days. Because of the many interactions among adrenal, thyroid, and testicular hormone axes, it is unclear whether the primary effect of short days is on one of these endocrine systems or on another factor that has separate effects on each of the hormone rhythms that was measured. Nonetheless, it is clear that a major effect of short day lengths in hamsters is to suppress hormone rhythms. Explanations of photoperiodic effects that depend on endocrine mediation should take this into account.

Adrenal Cortex Hormones↗

Testicular hormone concentration in men with varicoceles: immediate effects of varicocelectomy.

As part of an investigation of the role of gonadal steroid concentrations and testicular function, testosterone (T), estradiol (E2) and dehydroepiandrosterone sulfate (DHEA-S) were measured in bilateral testicular biopsies from infertile men with varicoceles. The biopsies were performed randomly either immediately before or 1 hour after varicocelectomy in an effort to detect acute changes in testicular hormone concentrations. No significant differences were noted between these two groups nor was there consistent evidence of disturbed in vivo Leydig cell function. A wide range of testicular hormone concentrations was found in these biopsies, which did not correlate well with morphologic findings. This suggests that many different pathophysiologic conditions may exist in association with the presence of a varicocele.

Biopsy↗

Testicular hormonal regulation of the renin-angiotensin system in the rat epididymis.

Evidence for the existence of an intrinsic angiotensin system based on locally formed angiotensinogen as a precursor for angiotensin production has been demonstrated in the rat epididymis. The data strongly support the presence of an epididymal renin-angiotensin system (RAS) which may be important for epididymal and sperm functions. In the present study, the effects of castration and testicular hormonal replacement on the expression of RAS components from the rat epididymis are investigated at the gene and protein levels. Results from northern blot and western blot analyses consistently showed that the expression of angiotensinogen mRNA and protein was apparently abolished by castration whereas their expression was completely restored to control levels when the castrated rats were hormonally replaced with either testosterone alone or with combined testosterone and estradiol. Northern blot did not detect any signal for angiotensinogen mRNA while western blot could detect a weak signal for angiotensinogen protein when the castrated rats were replaced with estradiol alone. Renin could be detected neither in control, castrated nor hormonally replaced rats. Moreover, the expression of angiotensin II receptor, type I (AT1) was almost abolished by castration as demonstrated by northern blot and reverse transcription-polymerase chain reaction. These data indicate that the expression of RAS by the rat epididymis at the levels of its precursor angiotensinogen and its receptor AT1, is subject to the regulation of testicular hormones and its expression appears to be predominantly testosterone-dependent.

Angiotensinogen↗

Acute effects of spinal cord injury on the pituitary-testicular hormone axis and Sertoli cell functions: a time course study.

The present study investigated the time course of the onset of the abnormalities in spermatogenesis following spinal cord injury, and their relationship to changes in the pituitary testicular hormonal axis and Sertoli cell function. Spinal cord injury (SCI) was induced in adult male rats by surgical transection of the spinal cord at the level of T9 and L1 vertebrae. Animals were killed 3, 7, and 14 days after the operation. As early as 3 days following SCI, abnormalities in spermatogenesis, including delayed spermiation and vacuolization of the nucleus of spermatids, were noted in both the T9 and L1 animals. By 14 days, other lesions, including phagocytosis of mature spermatids, incomplete cellular associations, and total regression of seminiferous epithelium, became apparent. Concurrently a transient but significant (P < 0.05) suppression of serum follicle-stimulating hormone (FSH) occurred in the T9 animals, and a suppression of serum luteinizing hormone (LH) occurred in both the T9 and the L1 animals 3 days after the surgery. This was accompanied by a suppression of testicular and serum testosterone levels (P < 0.05, P < 0.01, respectively). Most of the hormonal parameters had recovered and were not different from those of sham-operated animals by 14 days (P > 0.10). Northern blot analysis of testicular poly(A)+ RNA revealed a transient but significant reduction in the steady-state level of the 2.7-kilobase (kb) Sertoli cell transferrin mRNA transcript in both the T9 and the L1 animals 3 days after the operation (P < 0.05). On the other hand, the 1.7-kb androgen binding protein (ABP) mRNA remained unaffected during the 2-week study period. The steady-state level of mRNA transcripts for spermatogenic cell-specific hemiferrin and spermatid specific transition protein 2 and protamine 1 also remained unchanged. These results suggest that spinal cord injury will result in a temporary, but profound, effect on the pituitary-testicular hormone axis. These changes may impair certain aspects of Sertoli cell function that could render these cells incapable of supporting normal spermatogenesis. However, the severity of spermatogenic lesions and the disparate responses of the two major Sertoli cell proteins make it unlikely that hormone deficiency is the only mechanism responsible for the impaired spermatogenesis following spinal cord injury.

Androgen-Binding Protein↗

A kinematic analysis of sex-typical movement patterns used during evasive dodging to protect a food item: the role of testicular hormones.

Feeding rats dodge laterally away from a conspecific attempting to steal their food. Dodges by female and male rats differ in their composition of movement. Females pivot around a point more posterior on the longitudinal axis than do males, producing a greater amount of movement of the snout in relation to the pelvis. This experiment examined the role of testicular hormones on these sex-typical movement patterns. Castration at weaning (21 days) does not affect the male-typical pattern. Neonatal testicular hormone manipulation, however, does alter sex-typical patterns of movements. Whereas castration neonatally makes male rats more female-like, injections of neonatal female rats with testosterone propionate make them more male-like. These findings suggest that the organization of sex-typical patterns of dodging involves perinatal action of gonadal hormones. Results are discussed in relation to anatomy, neural structure, and the role of gonadal hormones during development.

Animals↗

Effect of flutamide or cyproterone acetate on pituitary and testicular hormones in normal men.

To test the effects of antiandrogen treatment on the endocrine system 20 normal young men were treated with 750 mg/day flutamide [4-nitro 3'-trifluoromethylisobutyranilide (FLU)] or 100 mg/day cyproterone acetate (CPA) for 14 days followed or preceded by a placebo treatment of the same duration 4 weeks apart. Allocation of both drugs and sequence of active and placebo substance was by random number in a double blind design. On days 1 and 14 two basal blood samples were obtained 15 min apart followed by an iv injection of 25 micrograms GnRH and 10 mg metoclopramide (MTCL). Subsequently blood samples were taken after 25, 45, 60, and 90 min. On day 8 the GnRH/MTCL test was performed after 13 basal blood samples were obtained to establish a baseline for PRL concentrations unbiased by short term stress. After 14 days of FLU treatment, serum testosterone (T) increased significantly [17.4 +/- 1.4 (SE) vs. 26.9 +/- 1.5 nmol/liter, as well as estradiol (E2) concentrations (144 +/- 12 vs. 177 +/- 20 pmol/liter). Dihydrotestosterone increased slightly after 14 days of FLU administration (1.59 +/- 0.14 vs. 1.98 +/- 0.30 nmol/liter). At the same time basal LH concentrations were significantly elevated (5.9 +/- 0.5 vs. 8.6 +/- 0.6 ng/ml), whereas FSH levels were not affected (2.8 +/- 0.6 vs. 2.8 +/- 0.6 ng/ml). No changes in PRL values were detected throughout treatment with FLU. The effect of CPA was quite different. At the end of the treatment phase, serum T levels were reduced considerably (14.6 +/- 1.8 vs. 3.3 +/- 0.4 nmol/liter). Serum E2 decreased similarly (95 +/- 13 vs. 35 +/- 6 pmol/liter). Conversion of T to dihydrotestosterone was also diminished significantly (1.72 +/- 0.33 vs. 1.14 +/- 0.33 nmol/liter). Both gonadotropins were significantly depressed after 14 days of CPA administration (LH, 5.6 +/- 0.7 vs. 2.8 +/- 0.4 ng/ml; FSH, 2.4 +/- 0.3 vs. 1.4 +/- 0.2 ng/ml). Basal PRL levels were not affected, although the response of MTCL was reduced at the end of the treatment phase. Both drugs reduced the response of LH and FSH to GnRH administration.

Adult↗

Importance of testicular hormones in maintaining the annual pattern of LH secretion in the male horse.

Serum LH was measured by radioimmunoassay in 5 long-term (greater than or equal to 3 years) castrated male horses bled at 30-min intervals for 2 h twice a month from March to February. There was no significant effect of month on LH levels; however, mean levels were significantly lower in spring than autumn (P less than 0.05). By contrast, stallions in the same environment showed a markedly seasonal pattern of LH secretion, with LH rising at the onset of the breeding season to reach levels in late spring 3-4 times those in early winter. Despite differences in seasonal patterns of secretion, annual mean LH levels in geldings (19.6 ng/ml) and stallions (20.4 ng/ml) were similar. In mid-summer, LH was measured in 6 geldings castrated 4-6 weeks previously, 25 geldings castrated 3-25 years previously, and 8 stallions; mean +/- s.e.m. LH values were 62.2 +/- 8.0, 14.0 +/- 1.6, and 13.0 +/- 2.2 ng/ml respectively. In the long-term geldings, LH was not affected by age, indicating that, after the rapid 4-fold post-castration rise, LH falls to within the normal range of pre-castration values and stabilizes. These results show that testicular hormones are necessary to maintain the normal seasonal pattern of LH secretion in the male horse, including the increase in LH at the onset of the breeding season. It is suggested that the effects of testicular hormones on LH secretion include (1) a negative feedback at the hypothalamus/pituitary as observed in other species, and (2) a positive component in the pathway by which LH is increased at the onset of the breeding season.

Androgens↗

Altered testicular hormone production in infertile patients with idiopathic oligoasthenospermia.

We studied the kinetics of testicular response to human chorionic gonadotropin (hCG) in oligoasthenospermic and asthenospermic patients (OAZ-AZ). The responses of testosterone (T), androstenedione (A), 17 OH-progesterone (17OHP), and estradiol (E2) were evaluated in 60 OAZ-AZ patients and compared to those of 10 normal men. The responses of T, A, and 17OHP to hCG in the control group displayed a biphasic pattern with an initial peak at 4 hours and a second peak after 24 hours. The E2 response showed a single peak between 24 and 48 hours after hCG administration. OAZ-AZ patients had two types of T responses: group 1 (n = 40) had no first peak and group 2 (n = 20) had a normal response pattern. The response of A was similar to that of T, and the E2 response was normal in both groups. There were three types of 17OHP responses in group 1 (low, high, or normal); however, the 17OHP response was normal in group 2. Treatment of group 1 with aromatase inhibitors (aminoglutethimide or testolactone) induced an improvement of the acute T response only in patients with high or normal 17OHP response to hCG, whereas no effects were observed in patients with low 17OHP response. In group 2, the aromatase inhibitors induced no changes in the T response. These results demonstrate that in some OAZ-AZ patients (group 1, blunted T response) testicular hormone production is altered. They also suggest the presence of two enzyme blocks: one at the 17,20 desmolase level, mediated by E2, and another at early biosynthetic steps, not mediated by E2.

Adult↗