Intracellular distribution of pregnenolone metabolites in testis of macaque (Macaca fascicularis).

The metabolism of pregnenolone in subcellular fractions of the testes of the macaque (Macaca fascicularis) has been studied using capillary gas chromatography to characterize and quantify the metabolites, after their conversion into the O-methyloxime and/or trimethylsilyl ether derivatives. The microsomal incubations yielded the greatest quantities of metabolites, with lesser amounts in the mitochondrial fraction. The cytosolic fraction contained no significant quantity of metabolites after incubation, except for 5alpha-androst-16-en-3 beta-ol. This, and other odorous androst-16-enes, found in the microsomal fraction, are of particular interest in the context of animal communication because of their possible pheromonal role. Pregnenolone was converted into androst-5-ene-3 beta,17 beta-diol, androst-4-ene-3,17-dione and testosterone, suggesting that both classical pathways for testosterone synthesis were operating. Testosterone was further converted into 5 alpha-reduced androstanediols, especially in the microsomal fraction.

Murine aggression induced by a boar chemosignal: a stimulus presentation dependency.

Male mice were used to assess for the presence of aggression-promoting cues in the boar chemosignal, 5 alpha-androst-16-ene-3-one. The findings of Experiment 1 indicated that this steroid has no aggression-promoting properties when mixed in water. When mixed in urine from castrated males, however, the steroid was shown to induce agonistic behavior in aggressors. Thus, the steroid was shown to possess aggression-promoting cues when associated with urine. Experiment 2 was designed to assess the chemosignal properties of the steroid when mixed in urine or juxtaposed either proximally or distally to urine. It was determined that the steroid needed to be either adjacent to or mixed in urine for chemosignal activity to be evidenced. It was concluded that (1) urine may function as an orienting stimulus for the appropriate detection of the steroid or (2) the conjoint presentation of the steroid and urine provided a qualitatively different stimulus complex than either stimulus presented alone. The findings of both experiments question the species specificity of the boar chemosignal and have methodological implications for studies attempting to isolate a chemocommunicative substance. Appropriate stimulus presentation procedures need to be considered for future research projects.

1. Estrogen antagonists. Aromatase inhibitors, their pharmacology and application.

Aromatase inhibitors, 4-OHA, 4-acetoxy-A and ATD cause competitive inhibition and inactivation of aromatase in vitro. The latter property may account for sustained aromatase inhibition observed in vivo, even though 4-OHA is cleared rapidly from the circulation. Thus, all 3 compounds inhibit the prosestrus oestrogen surge in rats. Treatment with 4-OHA for one oestrus cycle is sufficient to block ovulation for at least 10 additional days. Although ovarian oestrogen production was reduced by long-term inhibitor treatment, gonadotrophins remained at basal levels, suggesting a direct effect of 4-OHA on gonadotrophins. Marked regression of DMBA-induced mammary tumours occurred in rats treated with aromatase inhibitors. The compounds were more effective alone against these tumours than when combined with the antioestrogen, tamoxifen. Sustained antitumour effects of 4-OHA were observed in rats treated twice daily (50 mg/kg/day) for 9 days and twice weekly thereafter for 20 weeks. Tumours regressed during the first 9 days and 18/19 tumours remained suppressed for 20 weeks. The results in animal models suggest that highly potent aromatase inhibitors may be useful for breast cancer treatment and for other oestrogen related clinical problems.

Absence of HLA association or linkage for variations in sensitivity to the odor of androstenone.

Sensitivity to the odor of 5-androst-16-en-3-one (androstenone), a testosterone metabolite, shows wide variations among unrelated individuals. Analysis of correlations in sensitivity between monozygotic twin pairs, dizygotic twin pairs, and nontwin sib pairs now shows that at least a portion of this variation is genetically determined. However, although data from some mouse studies have suggested a relationship between olfaction and the murine histocompatibility system (H-2), we were unable to demonstrate any role of the human HLA system in explaining the wide individual variations in human sensitivity to androstenone. An additional analysis of HLA antigens among 61 human mating pairs also provided no evidence that HLA phenotypes play a role in human mating preference. These data fail to support a role for the human HLA system in the recognition of an odorant of potential biological significance.