The long term goal of this research is to define the mechanism(s) by which progesterone (P) increases prolactin secretion in estrogen (E)-primed nonhuman primates. Prolactin secretion has been used as an indicator of serotonin function and deficits in prolactin release have been reported for patients with major clinical depression. Therefore, understanding the neural pathway by which ovarian steroids regulate prolactin secretion may also reveal important information about the role of ovarian steroids in the neural control of depression. Lactotropes do not contain progestin receptors (PR) and hence the action of P on prolactin is probably mediated by the central nervous system. Our previous work suggests that the action of P on prolactin regulatory neurons is transduced by afferent neurons. We hypothesize that serotonin (5HT) stimulates b-endorphin (BE) and gamma amino butyric acid (GABA) neurons which, in turn, inhibit the arcuate dopamine neurons resulting in increased prolactin secretion. The 5HT2a and 2c receptors are stimulatory postsynaptic receptors. Therefore, we further hypothesize that BE and GABA neurons may express the 5HT2a and 2c receptors and that E and P may increase expression of these receptors in the hypothalamus. Studies are underway with in situ hybridization to determine whether monkeys treated with E or E+P express higher levels of the 5HT 2a and 2c receptors in the hypothalamus, frontal cortex and amygdala. An increase in these receptors would facilitate serotonergic transmission which, in turn, would elevate prolactin secretion and mood.
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