No abstract

In primates, plasma testosterone concentrations are elevated for some 3 months from birth. The function of this rise is uncertain, but studies in rats suggest that its prevention by castration or administration of gonadotrophin hormone-releasing hormone (GnRH) analogues has effects on development and expression of social and sexual behaviours, and adverse long-term effects on fertility. The consequences of suppression of this rise in testosterone by treatment with the GnRH antagonist antide have been investigated in the marmoset monkey. Eight sets of male:male twins were used, one of each set receiving s.c. injections of antide (10 mg/kg), on days 0, 3 and 7, then weekly from birth to 98 days of age, with the twin receiving vehicle only. Plasma samples were taken at weekly intervals for the determination of testosterone concentrations from birth until 2 years of age. Treatment with antide completely abolished the neonatal rise in testosterone seen in control animals. The timing of the onset of the pubertal testosterone rise was not significantly affected by treatment; however, the subsequent pattern of circulating testosterone showed a tendency to decreased plasma concentrations in the neonatally treated group from weeks 25 to 42, relative to controls, and this difference was significant between 43 and 70 weeks. This was associated with a similar depression in bioactive LH concentrations around this time. Thereafter, the testosterone concentrations were similar between treated and control groups. There was no effect of treatment on growth, based on sequential body weight data. At 20 months the animals underwent behaviour tests with ovariectomized females.(ABSTRACT TRUNCATED AT 250 WORDS)

Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas–liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP; 55%), followed by diethylphosphate (DEP; 46%), dimethylthiophosphate (DMTP; 32%), and dimethyldithiophosphate (DMDTP; 31%). However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%). The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamic–pituitary endocrine function and also indicates that FSH and LH are the hormones most affected.