The influence of prolonged cimetidine administration on serum gastrin levels and gastric acid secretion in rats.

The correlation between serum gastrin levels and gastric acid secretion during 4 weeks of cimetidine administration (once daily) was investigated. Serum gastrin levels and gastric acid secretion were estimated on the 7th, 14th, 21st and 28th day after cimetidine administration (25 mg.kg-1, intragastrically). At the mentioned time intervals gastric acid secretion stimulated by histamine and pentagastrin was also studied. It was found that on the 14th and 21st day after cimetidine administration serum gastrin levels were significantly elevated. Basal gastric acid secretion after cimetidine administration was significantly decreased at all the observed time intervals. Histamine-stimulated gastric acid secretion was increased on the 14th, 21st and 28th day after cimetidine administration. Hypoacidity was not followed at all time intervals by hypergastrinaemia (only on day 14 and 21 after cimetidine).     

Effect of underfeeding on the inhibition of gonadotrophin secretion by testosterone propionate in rats.

Single (0 . 25 mg/100 g body wt) or multiple (5 x 20 microgram/100 g) injections of testosterone propionate were given to castrated male rats fed normally or restricted to a 50% intake. Serum FSH and LH levels were higher in the underfed rats and the effectiveness of testosterone propionate in suppressing serum levels of gonadotrophins was increased by underfeeding.     

Subnormal serum testosterone levels in male internal medicine residents.

The consequences of sleep deprivation and stress in residency training have not been quantified. In the course of assembling a control group for other studies, we unexpectedly observed a significant (P less than 0.005) and marked depression of serum testosterone levels in healthy male internal medicine residents (means = 11.8 +/- 1.1 nmol/L, n = 7) compared with other hospital personnel (means = 20.6 +/- 5.3 nmol/L, n = 18). Testosterone concentrations in the two groups were entirely nonoverlapping, while luteinizing hormone levels were not significantly different. We conclude that the stress of residency training leads to a quantifiable depression of gonadal function, and that gonadal steroid concentrations may be useful in evaluating measures intended to reduce that stress.     

Adrenocorticotropin administration increases testosterone secretion in adult male rats

It appears that the effect of acute administration of pituitary-adrenal hormones on the pituitary-gonadal axis is species-dependent. However, no information is available with regard to the effect of acute adrenocorticotropin (ACTH) administration on testosterone secretion in rats. The present data indicate that acute ACTH administration can increase serum testosterone levels without modifying luteinizing hormone (LH) levels. Since this rise was not observed in castrated rats, it must be assumed that increased serum testosterone was of gonadal origin. The action of ACTH on testosterone secretion was likely an indirect one since there is no evidence at present for a direct, short-term action of the pituitary-adrenal axis on Leydig cell function.     

Effects of testosterone metabolites on serum gonadotropin concentrations in immature male rats.

The ability of testosterone, androsterone, 5alpha-androstane-3alpha,17beta-diol, and 5alpha-androstane-3beta,17beta-diol to prevent the castration-induced rise in serum gonadotropin levels was investigated in immature male rats. Rats castrated at 30 days of age were treated once per day by subcutaneous injection of 12.5-100 mug of the steroid per 100 g body weight per day for 3 days, beginning on the day of castration. The animals were sacrificed 24 h after the last injection. Testosterone propionate, androsterone propionate, and 5alpha-androstane-3alpha,17beta-diol dipropionate were also tested at the approximate molar equivalent of 100 mug of the free alcohol form per 100 g body weight per day. Testosterone propionate and 5alpha-androstane-3alpha,17beta-diol were the only compounds tested that prevented the castration induced rise in luteinizing hormone (LH) concentrations. Testosterone propionate also inhibited the rise in follicle stimulating hormone (FSH) concentrations whereas 5alpha-androstane-3alpha,17beta-diol inhibited the rise in FSH in one but not in another experiment. These were the only compounds tested that affected serum FSH concentrations. The lower doses of testosterone tested significantly increased serum LH, but not FSH concentrations compared to castrate control animals. The highest dose tested partially inhibited the rise in serum LH concentrations. Both androsterone and androsterone propionate maintained ventral prostate weights. Although neither compound prevented the castration induced rise in serum LH, two groups receiving androsterone had serum LH concentrations significantly lower than the castrate control group. 5alpha-Androstane-3beta,17beta-diol and 5alpha-androstane-3alpha,17beta-diol dipropionate failed to maintain ventral prostate weights or prevent the rise in serum gonadotropin levels. These results indicate that 5alpha-androstane-3alpha,17beta-diol is capable of preventing the castration induced rise in serum LH concentrations in the immature male rat and thus may participate in the regulation of LH secretion in these animals.     

The relationship between circulating testosterone levels and male sexual behavior in rats

The relationships between plasma testosterone (T) and various parameters of male sexual behavior were examined in intact and castrated T-treated male rats. Repeated blood sampling and behavioral testing revealed no correlation between any measure of sexual behavior and plasma T in normal untreated sexually active males. T-Filled Silastic capsules, implanted subcutaneously at the time of castration, were found to produce plasma T levels proportional to capsule size. Plasma T titers less than 10% of normal (0.2 ng/ml) maintained ejaculatory behavior near normal levels for the 58 days of the experiment. Measures of sexual behavior which showed androgen dependence were intromission latency, postejaculatory interval, and intromission frequency. The plasma T concentration required to maintain these parameters within the intact range was 0.7 ng/ml, which is less than one-third of the mean intact level (2.6 ng/ml). No significant improvement in the sex behavior measures was seen with plasma T levels between 0.7 and 3.1 ng/ml. It was concluded that the absence of relationships between circulating T and sexual behavior in the normal rat population is due to the androgen requirement for this behavior being less than the amount normally present. Findings on T levels and T treatment in noncopulator males are also presented.     

Effect of coitus on serum levels of testosterone and LH in male and female rabbits.

Levels of testosterone (T) and LH in the peripheral serum of male and female rabbits were measured and compared following coitus. Blood was collected by heart puncture from restrained, unanesthetized animals of both sexes. In male rabbits, basal serum T levels were highly variable, ranging from 131 to 12,149 pg/ml, and if low preceding coitus they tended to rise; whereas, if high, they usually dropped as they did in nonmated males subjected to repeated heart punctures. In contrast, basal serum LH levels in males were quite constant (mean +/- SE, 1993 +/- 152 pg/ml) and were not significantly altered after coitus unless blood T levels had been drastically lowered by two priming doses of estradiol benzoate. In intact does, on the other hand, copulation which resulted in ovulation induced an approximately 20-fold increase in serum LH concentration which was sustained for about 4 hr. Postcoital elevations in serum LH also occurred in estrogen-primed intact and estrogen-primed ovariectomized does. Under the conditions of our experiments, the parallel elevations in serum LH and T observed postcoitally in the female rabbit could not be demonstrated in the male.     

Acute effects of testosterone on serum PGE2 levels in male dogs

Serum prostaglandin levels are influenced by testosterone. To test the hypothesis that the effect of testosterone is mediated through the prostate gland, testosterone was given acutely to intact and to prostatectomized male dogs. Intact dogs responded to testosterone with an abrupt, transient rise in plasma PGE2 levels; prostatectomized dogs did not respond. We conclude that testosterone has an acute effect on the prostate gland which results in release of PGE2 into the blood stream.     

Genistein administration decreases serum corticosterone and testosterone levels in rats

The phytochemical flavonoid genistein has been shown to act as a potent competitive inhibitor of human adrenocortical 3beta-hydroxysteroid dehydrogenase and cytochrome P450 21-hydroxylase activities in vitro [J. Steroid Biochem. Molec. Biol. 2002; 80: 355-363]. In the present study, we evaluated the effects of large amounts of genistein continuously administered to weanling rats, particularly on steroidogenesis at the pubertal stage in vivo. Serum concentrations of free and total genistein were significantly higher in the 40 mg/kg genistein administration group when compared with the control group. In genistein administered rats, adrenal weight was significantly higher. Furthermore, a clear expansion of cells was observed in hematoxylin and eosin stained tissue at the zona fasciculata and zona reticularis of the adrenal cortex. However in the testis, no differences in weights or histologic changes were observed. Serum corticosterone concentration significantly decreased to 50% of control levels by 40 mg/kg genistein administration and testosterone also tended to decrease with this dose of genistein. On the other hand, although serum follicle stimulating hormone was unchanged, adrenocorticotropic hormone and luteinizing hormone levels increased with genistein administration. These results suggest a significant effect of genistein on steroidogenesis in the adrenal gland and testis of rats, and this effect appeared to be more evident on steroid production in adrenals than in testis in vivo.     

Regulation of gonadotrophin secretion in rams from birth to sexual maturity. I. Plasma LH, FSH and testosterone levels.

Plasma LH, FSH and testosterone concentrations were measured by radioimmunoassays in male crossbred Merino/Corriedale sheep from birth to 45 weeks of age. FSH levels were 11 and 22 ng/ml at birth, increased to peak levels (mean value of 47 ng/ml) at 5 weeks and fluctuated between 25 and 35 ng/ml for the next 40 weeks. Similarly, LH (less than 0-5 ng/ml) and testosterone (less than 38 ng/100 ml) levels were low at birth and were significantly elevated by 5 weeks of age. LH values varied betwen 0-9 and 3-0 ng/ml for the next 30 weeks and then a secondary rise occurred reaching levels of 2-4 ng/ml by the 41st week after birth. Concentrations of LH subsequently fell to levels observed in adult rams. Testosterone levels rose gradually between the 5th and the 25th week, and then increased rapidly to values of 270-517 ng/100 ml by the 41st week after birth, a time coincident with the peak LH levels. Histological examination of testicular biopsies demonstrated that Sertoli cell maturation occurred 17-21 weeks after birth and was followed by activation of spermatogenesis leading to the presence of spermatozoa in the seminiferous epithelium by 39-42 weeks of age.     

Diurnal variations of serum testosterone levels in intact and gonadectomized male and female rhesus monkeys.

A radioimmunoassay for serum testosterone which does not require chromatographic separation was used to measure the diurnal variations in intact and orchidecomized males and intact and ovariectomized females. The intact male rhesus monkey shows a distinctive diurnal variation in serum levels of testosterone characterized by lower values during the day and a marked increase in the early evening (1900-2200 hr). The testosterone levels remain high throughout most of the lights-off period in the intact male. In contrast to the intact male, the markedly lowered serum levels of testosterone in the orchidectomized male were higher during the day and consistently showed a nadir during the early evening (2000-2200 hr). The evening nadir of testosterone levels was 51.0% lower than the 24-hr mean whereas the maximum serum level was 46.4% higher. A similar circadian pattern of testosterone was seen in both the intact and ovariectomized females. The testosterone values were higher during the day and consistently showed a nadir during the early evening. These results suggest that the adrenal secretion of testosterone varies in a diurnal pattern characterized by an early evening nadir. This adrenal pattern is overshadowed by a much larger gonadal rhythm in the intact male.     

Effect of carbohydrate-enriched diet and subsequent food restriction on life prolongation in Fischer 344 male rats

Increased proportion of carbohydrates (dextrin) in the diet has a life prolonging effect upon male Fischer 344 rats; however, the effect of this diet appears only when the rats aged from 6 weeks to 6 months are on diet, after this treatment median survival of experimental animals increases by 96 days and the 10th percentile increases on the average by 10 days (n-60). Further maintenance of animals on the same diet has minimum effect: animals being on this diet throughout the whole life exhibit a median lifespan increase by 120 days and an increase in the 10th percentile by 41 days. However, if such animals aged 6 months are transferred to a restricted (60%) food intake regimen (control diet, not enriched with carbohydrate) a further increase in median and 10th percentile lifespan prolongation can be observed reaching 328 and 396 days, respectively as compared to controls. The effects of this early feeding (from 6 weeks to 6 months) with a carbohydrate-enriched diet available ad libitum and food restricted (60% controls) regimen fed from the age of 6 months onwards are additive, the final results being identical as if the animals are kept on the 60% food restricted intake throughout the whole life.     

Effect of testosterone on serum immunoactive inhibin concentrations in intact and hypophysectomized male rats

Intact and hypophysectomized rats were treated with graded doses of testosterone via subcutaneous Silastic implants over a 13-week period. Serum inhibin concentrations fell 50% (P less than 0.001) after 2 weeks of hypophysectomy, remaining suppressed at this level for 13 weeks. The administration of testosterone to hypophysectomized rats (serum testosterone values 2-12 ng/ml; control values 5.5 ng/ml) was without effect on serum inhibin values. In contrast, administration of testosterone to intact animals for 7 weeks resulted in an initial fall (P less than 0.05) in inhibin levels to 50-70% of controls then increasing to reach control levels at higher doses. Serum FSH concentrations were similarly biphasic with increasing dose of testosterone and values for these two hormones were significantly correlated (r = 0.44, P less than 0.01). Segments of seminiferous tubules in culture from rats after various times of hypophysectomy showed a partly suppressed secretion of inhibin. The administration of testosterone did not modify inhibin production although inhibin production was sensitive to FSH. It is concluded that (1) serum inhibin concentrations are partly suppressed after hypophysectomy and testosterone has no effect on serum inhibin values; and (2) the suppression of serum inhibin in intact rats treated with increasing doses of testosterone is attributable to the concomitant fall in serum FSH concentrations.     

Effects of hCG on serum levels of testosterone, dihydrotestosterone and androstenedione in male mice

The concentrations of testosterone (T), 5alpha-dihydrotestosterone (5alpha-DHT) and delta4-androstenedione (delta4 A) in the circulating blood were increased by a single subcutaneous injection of 10 IU of hCG in the mouse. The response of androgen synthesis to hCG stimulation was rapid and persisted over a period of 96 h. The increased supply of T to the peripheral organ(s) under the stimulation of hCG might contribute to an increase in circulating 5alpha-DHT. However, the changes in T/5alpha-DHT ratio implies that the stimulation of T and 5alpha-DHT production by hCG were not of the same degree.     

Increases in testosterone levels and in copulatory behavior of male rhesus monkeys following treatment with human chorionic gonadotrophin

The sexual behavior of five male rhesus monkeys was observed before, during, and after administration of human chorionic gonadotropin (HCG) sufficient to induce increases in serum testosterone. Each male was given 12 half-hour pair tests with an estrogen-implanted ovariectomized female during each of the three phases of the study (Pretreatment, Treatment, Post-treatment). Summaries of selected categories of sexual and other social behaviors were tabulated for each phase of the study. Grooming, mount latency, and ejaculation frequency, as well as other behavioral measures, were unaffected by hormone treatment. However, latency to ejaculation decreased by 40% (P < 0.01) and mount rate increased by 71% (P < 0.05) during hormone administration. Sexual presentations by the female decreased by 38% (P < 0.05). Limb shaking decreased 55% during HCG treatment (P < 0.05). These findings demonstrate that increases in testosterone secretion subsequent to gonadotrophin injection in intact male rhesus monkeys can produce significant alterations in male and female sexual behavior.