The hypothesis to be tested is that the gender difference in the prolactin secretory response to Orphanin FQ/Nociceptin (OFQ/N) is due to neuromodulatory effects of the ovarian steroid hormones. Specifically, estrogen and/or progesterone modulate OFQ/N-induced prolactin secretion by acting, at least in part, on hypothalamic dopaminergic neural pathways. Dose response and time course studies of the prolactin secretory response to OFQ/N will be performed in ovariectomized (ovx) +/- steroid replaced female Sprague- Dawley rats. The response of the 3 major hypothalamic, dopaminergic neural systems to a minimum stimulatory dose of OFQ/N will be determined by HPLC/ECD in diestrous females and males and in the ovx +/- steroid treated groups. Regional specificity of the response will be examined. The role of serotonin and Thyrotropin Releasing Hormone (TRH) in sustaining the prolactin response will be determined by quantifying hypothalamic serotonergic activity in these same animals, by pharmacological blockade of serotonin receptors and by TRH immunoneutralization. The hypothesis is that following a brief, transient inhibition of the TIDA neurons, the sustained prolactin increase is due to releasing factors, i.e. serotonin and/or TRH. Finally, specificity of OFQ/N action will be demonstrated pharmacologically or by pretreatment with OP4 receptor antisense oligonucleotides. Our long-term objective is to understand the physiological significance of opiate regulation of prolactin secretion, particularly the role of OFQ/N and its modulation by ovarian steroids. Prolactin is an important anterior pituitary hormone that has over 300 separate biological activities. Prolactin is not only necessary for lactation in mammals, but also plays other, important roles in reproduction. Furthermore, it is important in mediating the stress response, maintaining immunocompetence and even maintaining homeostasis. Because prolactin has numerous, important physiological effects, determining the role of gonadal steroids in prolactin regulation will provide insight into our understanding of the mechanisms involved in the gender differences in physiological responses. To understand reproductive and stress-related disorders, it is important to understand the regulation of prolactin secretion, including control by the endogenous opiates, which have potent, physiological effects on this hormone.
| Kalyani, Manu; Callahan, Phyllis; Janik, James M et al. (2017) Effects of Pup Separation on Stress Response in Postpartum Female Rats. Int J Mol Sci 18: |
| Kalyani, Manu; Hasselfeld, Kathryn; Janik, James M et al. (2016) Effects of High-Fat Diet on Stress Response in Male and Female Wildtype and Prolactin Knockout Mice. PLoS One 11:e0166416 |
| Chesterfield, Matthew; Janik, James; Murphree, Emily et al. (2006) Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in female rats. Endocrinology 147:5087-93 |
