Abstract
The pituitary gland hormone prolactin (PRL) regulates diverse physiological functions in the female mammal. PRL is secreted into peripheral circulation by lactotrophs in the anterior lobe of the pituitary gland. The primary physiological regulator of PRL secretion is Dopamine (DA). Three populations of neuroendocrine DAergic neurons (NDNs) with cell bodies in the periventricular (PEVN) and arcuate (ARN) nuclei of the hypothalamus release DA. During the 4-5 day estrous cycle of the rat, PRL secretion peaks on the afternoon of proestrus, due to a gradual rise in circulating ovarian steroids. Experiments show that the proestrous afternoon rise in PRL is timed by inputs from the biological clock located in the suprachiasmatic nucleus (SCN). Studies verify that disruption of the connection between SCN and its targets within the hypothalamus disrupt the timing of PRL secretion. Recently, it has been shown that the oscillatory function of the SCN occurs due to autoregulatory negative feedback loops of transcription factor expression within SCN neurons. These transcription factors are referred to as “clock genes”. Clock genes drive cell autonomous oscillations of gene expression and activity in the SCN and additional areas of the CNS, coordinating rhythms of physiological activity. Given that the timing of PRL secretion appears to be regulated by the SCN and that NDNs receive direct input from the SCN, I hypothesized that circadian rhythms of activity in NDNs time PRL secretion in the ovariectomized (OVX) rat. I have shown that NDNs exhibit circadian and semi-circadian rhythms of activity that are modulated by ovarian steroid hormones. Further, I have determined the light-entrained and free-running rhythms of clock gene expression in NDNs. In addition, I have found that antisense knockdown of several clock genes in the SCN modulates, but fails to abolish, circadian rhythms of NDN activity. Results from these experiments, in agreement with previous work, reveal that NDNs display circadian and semi-circadian rhythms of DA release, driven by direct influence from the SCN. My results suggest a functional link between the expression of clock genes within SCN neurons and NDNs in the control of circadian rhythms of DA release and PRL secretion in the female mammal.
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