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 and gamma amino butyric acid (GABA) neurons which, in turn, inhibit the arcuate dopamine neurons resulting in increased prolactin secretion. We have shown that E increases the expression of the mRNAs for tryptophan hydroxylase and the serotonin reuptake transporter, but addition of P had no further effect. However, E+P does cause a further decrease in the expression of the 5HT1a autoreceptor. Together the actions of E and P would increase 5HT synthesis, decrease 5HT reuptake (elevate 5HT in the synapse) and permit 5HT neuronal firing to increase. These effects of E and P would also elevate mood.
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