NEUROENDOCRINE MEDIATION OF SOCIALLY INDUCED ANOVULATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Studies have continued this year assessing the consequences of psychosocial stress, resulting from social subordination, on metabolic, reproductive, and behavioral outcomes in adult female rhesus monkeys. In addition, the contribution of polymorphisms in the gene that encodes the serotonin reuptake transporter (5HTT) was evaluated as other studies show individuals carrying one or both alleles of the short promoter length variant (s-variant) are more vulnerable to the adverse consequences of psychosocial stress than females homozygous for the long promoter length (l/l). During the current year, studies show that the reproductive compromise experienced by subordinate females is due to enhanced estradiol negative feedback inhibition of LH secretion. Indeed, this hypersensitivity was further enhanced in subordinate females with the short promoter length polymorphism (s-variant) is the 5HTT gene. Follow-up studies showed that positive feedback of estradiol, necessary to stimulate ovulation, is unaffected by subordination. These data indicate that psychosocial stress may increase infertility in women by disruption mechanisms responsible for follicular maturation. Other studies use PET neuroimaging to test the hypotheses that GABAergic receptor subtype A would be diminished in subordinate s-variant females in brain regions associated with stress reactivity. All PET scans were completed in Nov 2009 and analyses are underway. Additional studies used automated feeders to quantify intake of standard low fat, high fiber monkey chow in socially housed females to better understand the metabolic deficits observed in subordinates. Activity levels, as a surrogate measure of energy expenditure were measured for one week in all females. Data indicate that subordinates, regardless of genotype, eat less of the low fat, high fiber diet than dominant animals and show similar amounts of activity. The data indicate that the hypometabolic condition associated with subordination is due to reduced food intake and more energy expenditure per calorie of food consumed. These studies provide insights into possible treatment strategies for women suffering from stress-induced infertility.