Michael Selmanoff, Ph.D.
Laboratory of Reproductive Neuroendocrinology
This research program seeks to determine the neuroendocrine mechanisms regulating luteinizing hormone (LH) and prolactin (PRL) secretion in mammals. Ongoing studies are examining hypothalamic mechanisms by which testosterone in males, and 17b -estradiol plus progesterone in females, inhibit GnRH pulse generator function. A current focus of ours is on the role of steroid-concentrating GABAergic neurons in this regulation. GABAergic neurons situated in the rostral medial preoptic nucleus, the sexually dimorphic nucleus of the preoptic area and the tuberoinfundibular GABAergic neurons are under most active study. Elevated levels of PRL also suppress the neuroendocrine mechanisms responsible for tonic (male and female) and cyclic (female) LH secretion in mammals. In addition to being fundamental questions in reproductive neurobiology, these antagonisms between sex steroids and LH, and PRL and LH, have profound contraceptive significance. This research will further our understanding of the hypothalamic mechanisms regulating LH and PRL secretion, and the ways in which negative feedback steroids and elevated circulating PRL levels affect these mechanisms.
Trainees involved in these projects obtain experience with several techniques and experimental approaches including: (1) determination of neurotransmitter and neuropeptide turnover in microdissected hypothalamic structures, (2) stereotaxic microcannula placement for microinfusions (i.e. 100-500 nl) of steroid receptor antagonists and receptor mRNA antisense oligonucleotides into discrete steroid-sensitive hypothalamic sites, (3) determination of pulsatile GnRH release in push-pull perfusates of the anterior pituitary gland in awake, freely behaving animals, (4) single- and double-label quantitative in situ hybridization histochemistry at the single cell level, (5) immediate early gene mRNA induction and immunohistochemistry, and (6), microlysate RNase protection assay. Experience with these and other methods is intended to develop in trainees the ability to be creative and critical experimental neurobiologists in the future.
Recent PublicationsSagrillo CA, Grattan DR, McCarthy MM, Selmanoff M 1996 Hormonal regulation of GnRH gene expression and related reproductive behaviors. Behav Genet 26:241-277.
Grattan DR, Rocca MS, Sagrillo CA, McCarthy MM, Selmanoff M 1996 Antiandrogen microimplants into the rostral medial preoptic area decrease g -aminobutyric acidergic neuronal activity and increase luteinizing hormone secretion in the intact male rat. Endocrinology 137:4167-4173.
Sagrillo CA, Selmanoff M 1997 Castration decreases single cell levels of mRNA encoding glutamic acid decarboxylase in the diagonal band of Broca and the sexually dimorphic nucleus of the preoptic area. J Neuroendocrinol 9:699-706.
Grattan DR, Selmanoff M 1997 Sex differences in the activity of g -aminobutyric acidergic neurons in the rat hypothalamus. Brain Research, in press.
Selmanoff M 1997 Prolactin inhibitory factors. In: Encyclopedia of Reproduction, E. Knobil and J. D. Neill (Eds), Academic Press/New York, pp 000-000, in press.
