The ultimate objective of this research program is to understand how androgens modulate brain function and regulate the expression of male sexual behavior (MSB). Our approach is to employ biochemical and molecular techniques in combination with behavioral studies to address questions on androgen action in male rat brain. We have expanded our behavioral investigations to include androgen-dependent measures such as partner preference, vocalization and anogenital investigation. All of these behaviors, along with copulation itself, are influential in the expression of MSB and will be referred to herein as androgen-dependent sexual behaviors. To achieve our goals, we will investigate three questions. Question l focusses on the neural sites of androgen action in regulating androgen-dependent sexual behaviors. The androgen receptor (AR) blocker, hydroxyflutamide (OHF), will be used to assess the role of AR in mediating androgen-dependent sexual behaviors in two previously unstudied androgen- concentrating brain sites: the ventromedial hypothalamic nucleus (VMN) and cranial nerve motor nuclei (n. ambiguous, hypoglossal n., facial motor n.). Question 2 focusses on the controversy over whether MSB is mediated by testosterone (T) acting via AR, or by aromatization to estradiol (E2). We will extend our recent results showing that both T and E2 are essential for MSB, by employing a newER blocker, RU58668, to assess the role of estrogen receptors (ER) in mediating androgen-dependent sexual behaviors. The site specificity of E2 action will be determined by implanting RU58668 directly into the medial preoptic area (MPOA), VMN or medial amygdala. Question 3 focusses on the identification of androgen-dependent genes in the hypothalamus-preoptic area (HYP-POA). We will use a subtractively hybridized probe to screen our HYP-POA cDNA library from T-treated adult male rats. RNAse protection assays will be used to verify that the isolated clones are androgen-dependent. Confirmed androgen- dependent clones will be sequenced to establish their identity. The answers to the three questions posed above are central to determining the consequences of T exposure in critical brain sites necessary for MSB, to resolving the controversy over the specificity of T action in the expression of androgen-dependent sexual behaviors, and will provide new insights into the cellular effects of T exposure. The results will also provide important knowledge on the effects of AR and ER blockers on behavior, which has clinical relevance for treating patients suffering from hormone-dependent tumors or from hormonal or sexual dysfunction.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD027727-06A1
Application #
2404404
Study Section
Special Emphasis Panel (ZRG2-BPO (01))
Project Start
1992-02-01
Project End
2002-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Cunningham, Rebecca L; Lumia, Augustus R; McGinnis, Marilyn Y (2013) Androgenic anabolic steroid exposure during adolescence: ramifications for brain development and behavior. Horm Behav 64:350-6
Harding, Shannon M; McGinnis, Marilyn Y (2004) Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors. Physiol Behav 81:671-80
McGinnis, Marilyn Y; Vakulenko, M (2003) Characterization of 50-kHz ultrasonic vocalizations in male and female rats. Physiol Behav 80:81-8
Harding, Shannon M; McGinnis, Marilyn Y (2003) Effects of testosterone in the VMN on copulation, partner preference, and vocalizations in male rats. Horm Behav 43:327-35
McGinnis, Marilyn Y; Montana, Robert C; Lumia, Augustus R (2002) Effects of hydroxyflutamide in the medial preoptic area or lateral septum on reproductive behaviors in male rats. Brain Res Bull 59:227-34
Yu, W H; McGinnis, M Y (2001) Androgen receptors in cranial nerve motor nuclei of male and female rats. J Neurobiol 46:1-10
Vagell, M E; McGinnis, M Y (1998) The role of gonadal steroid receptor activation in the restoration of sociosexual behavior in adult male rats. Horm Behav 33:163-79
McGinnis, M Y; Kahn, D F (1997) Inhibition of male sexual behavior by intracranial implants of the protein synthesis inhibitor anisomycin into the medial preoptic area of the rat. Horm Behav 31:15-23
Vagell, M E; McGinnis, M Y (1997) The role of aromatization in the restoration of male rat reproductive behavior. J Neuroendocrinol 9:415-21
Vagell, M E; McGinnis, M Y (1997) Inhibition of brain oestrogen receptors by RU 58668. J Neuroendocrinol 9:797-800

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