There are two main objectives to the research outlined in this application. The neural processes by which steroid hormones act to regulate female rodent sexual behavior will be studied. In addition, the relationship between steroid hormone-sensitive cells and neurotransmitterswill be investigated. The experiments in this proposal will add to our understanding of the cellular mechanisms by which the sex steroid hormones act on the central nervous system. The research makes use of a multidisciplinary approach including techniques of endocrinology, behavior, neuroanatomy and neuropharmacology. These experiments will require that some state-of-the-art neuroanatomical techniques be learned including immunocytochemistry and steroid autoradiography. These techniques will then be applied to the study of neurotransmitter-hormone interactions. Progesterone's effect on lordosis is used as a model neuroendocrine system, because progesterone has a unique, biphasic effect on this behavior, and because lordosis is a reliable, easily quantified, biologically-relevent, behavioral end-point of hormone action. In gonadectomized female rodents, progesterone synergizes with estradiol and induces a subsequent desensitization to progesterone. The role of the progestin receptor system in mediating progesterone's effects on this behavior, the regulation of the progestin receptor system, as well as an alternative mechanism of action for progesterone will be studied. The hypothesis that progesterone's desensitization effect, like its facilitatory effect, is involved in the regulation of sexual behavior during the estrous cycle of rodents will also be tested. Experiments to study the modulation of neural steroid hormone receptors by neurotransmitters are also described. These experiments are designed to study the regulation of steroid hormone receptors by neurotransmitters and of the neuroanatomical relationships involved in this regulation. Using a variety of neuroanatomical techniques, some characteristics of the cells that interact with estrogen- and progestin-sensitive cells will be determined. The hypothesis, that the regulation of steroid hormone receptors by neurotransmitters has functional significance for behavior, will be tested. The question of which neurotransmitters are present in progestinsensitive cells will also be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Modified Research Career Development Award (K04)
Project #
5K04NS000970-04
Application #
3074822
Study Section
Biopsychology Study Section (BPO)
Project Start
1985-09-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Massachusetts Amherst
Department
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003
Olster, D H; Blaustein, J D (1991) Development of estradiol-induced progestin receptor immunoreactivity in the hypothalamus of female guinea pigs. J Neurobiol 22:195-203
Tetel, M J; Blaustein, J D (1991) Immunocytochemical evidence for noradrenergic regulation of estrogen receptor concentrations in the guinea pig hypothalamus. Brain Res 565:321-9
Blaustein, J D; Nielsen, K H; Delville, Y et al. (1991) Neuroanatomical relationships of substance P and sex steroid hormone-sensitive neurons involved in sexual behavior. Ann N Y Acad Sci 632:314-31
Olster, D H; Blaustein, J D (1991) Progesterone facilitates lordosis, but not LH release, in estradiol pulse-primed male rats. Physiol Behav 50:237-42
Brown, T J; Blaustein, J D; Hochberg, R B et al. (1991) Estrogen receptor binding in regions of the rat hypothalamus and preoptic area after inhibition of dopamine-beta-hydroxylase. Brain Res 549:260-7
Delville, Y; Blaustein, J D (1991) A site for estradiol priming of progesterone-facilitated sexual receptivity in the ventrolateral hypothalamus of female guinea pigs. Brain Res 559:191-9
Bittman, E L; Blaustein, J D (1990) Effects of day length on sheep neuroendocrine estrogen and progestin receptors. Am J Physiol 258:R135-42
Blaustein, J D; Turcotte, J C (1990) Down-regulation of progestin receptors in guinea pig brain: new findings using an immunocytochemical technique. J Neurobiol 21:675-85
Olster, D H; Blaustein, J D (1990) Immunocytochemical colocalization of progestin receptors and beta-endorphin or enkephalin in the hypothalamus of female guinea pigs. J Neurobiol 21:768-80
Nielsen, K H; Blaustein, J D (1990) Many progestin receptor-containing neurons in the guinea pig ventrolateral hypothalamus contain substance P: immunocytochemical evidence. Brain Res 517:175-81

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