The long-term goal of this research is to understand neural control of reproductive maturation in males by investigating the interactions between gonadal steroid hormones, steroid-sensitive neural circuits, and peptidergic neuronal systems that initiate the frequent secretion of luteinizing hormone-releasing hormone (LHRH) at the time of puberty. The importance of frequent pulsatile release of LHRH to the onset of gonadal maturation in male humans is well-appreciated. Delayed puberty caused by deficient hypothalamic secretion of LHRH can be treated with pulsatile infusion of LHRH. However, the etiology of this hypothalamic malfunction is not understood. The initiation of frequent release of LHRH at puberty is due in part to a decrease in hypothalamic responsiveness to negative feedback effects of testosterone. Conversely, the pubertal activation of male sexual behavior results in part from an increase in central nervous system responsiveness to behavioral effects of testosterone. Concurrent with these alterations in steroid hormone action within the nervous system are neuroanatomical changes in LHRH-producing neurons and in endogenous opiate-producing neurons.
The specific aims of this project are to 1) identify both the mechanisms that contribute to and the functional significance of previously documented changes within the LHRH and beta-endorphin neuronal systems that occur during activation of the hypothalamic-pituitary-gonadal axis at the time of puberty; 2) investigate heterogeneity of function among LHRH neurons in order to differentiate LHRH neurons that regulate gonadotropin secretion from those that perform functions within the central nervous system within the context of puberty; and, 3) investigate region-specific regulation of steroid receptors by steroid hormones as a possible cellular mechanism for the pubertal shifts in responsiveness to testosterone.
These specific aims will be accomplished by a multidisciplinary approach that includes the use of immunocytochemical identification of peptidergic and steroid receptive neurons, in situ hybridization histochemistry for LHRH messenger RNA, neuronal tract tracing, and in vivo pharmacological manipulations.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD026483-05
Application #
2199970
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1989-12-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Michigan State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
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Romeo, Russell D; Richardson, Heather N; Sisk, Cheryl L (2002) Puberty and the maturation of the male brain and sexual behavior: recasting a behavioral potential. Neurosci Biobehav Rev 26:381-91
Sisk, C L; Richardson, H N; Chappell, P E et al. (2001) In vivo gonadotropin-releasing hormone secretion in female rats during peripubertal development and on proestrus. Endocrinology 142:2929-36
Parfitt, D B; Thompson, R C; Richardson, H N et al. (1999) GnRH mRNA increases with puberty in the male Syrian hamster brain. J Neuroendocrinol 11:621-7
Richardson, H N; Romeo, R D; Sisk, C L (1999) Regional changes in GnRH immunoreactivity with puberty in the male Syrian hamster. Brain Res 817:232-5
McElhinny, T L; Sisk, C L; Holekamp, K E et al. (1999) A morning surge in plasma luteinizing hormone coincides with elevated Fos expression in gonadotropin-releasing hormone-immunoreactive neurons in the diurnal rodent, Arvicanthis niloticus. Biol Reprod 61:1115-22
Meek, L R; Romeo, R D; Novak, C M et al. (1997) Actions of testosterone in prepubertal and postpubertal male hamsters: dissociation of effects on reproductive behavior and brain androgen receptor immunoreactivity. Horm Behav 31:75-88
Tang, Y P; Kashon, M L; Sisk, C L (1997) Brain region-specific regulation of luteinizing hormone-releasing hormone messenger ribonucleic acid in the male ferret: interactions between pubertal maturation and testosterone. Endocrinology 138:4740-7
Kashon, M L; Arbogast, J A; Sisk, C L (1996) Distribution and hormonal regulation of androgen receptor immunoreactivity in the forebrain of the male European ferret. J Comp Neurol 376:567-86
Kashon, M L; Hayes, M J; Shek, P P et al. (1995) Regulation of brain androgen receptor immunoreactivity by androgen in prepubertal male ferrets. Biol Reprod 52:1198-205

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