Meeting Abstract
The hypothalamus is a primary site for the integration of information that regulates reproductive function. In response to cues of psychological and metabolic stress, the hypothalamus decreases production and release of gonadotropins to decrease ovarian stimulation. However, the ovary itself expresses receptors to many of the same hormonal and chemical signals as the hypothalamus, and may modulate steroid production directly in response to such cues. We used in vitro culture experiments, hormone analysis, and quantification of gene expression to develop a comprehensive understanding of how mouse ovaries, even in the presence of gonadotropin stimulation, respond to specific physiological cues of stress. After 6 hrs of exposure to 400 ng/ml corticosterone (CORT), ovaries decreased progesterone production (P=0.03; n=6). In contrast, after exposure to 5 mM 2-Deoxy-D-Glucose (2-DG), a pharmacological agent that mimics hypoglycemia, ovaries increased progesterone production (P=0.04; n=5). There was no change in steroidogenic enzyme expression in ovaries exposed to CORT, while there was an increase in StAR (P=0.01) and P450scc (P=0.02) expression in ovaries exposed to 2-DG. Elevated production of progesterone in response to 2-DG treatment is consistent with the role for progesterone in glucose regulation. However, the mechanism by which glucose regulates progesterone production is unknown. Elevated progesterone production by ovaries exposed to 2-DG concomitant with an increase in StAR and P450scc expression demonstrates that ovarian steroidogenesis pathways can respond directly to metabolic cues, even when gonadotropin stimulation is high. Ultimately, these findings demonstrate that the ovary has the capacity to integrate metabolic cues alongside gonadotropin cues from the brain and pituitary.
