The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock that is critical in the temporal organization of circadian activity. The SCN coordinates the rhythmic secretion of gonadal hormones, and in turn, reproductive hormones may act on their receptors within the SCN to alter circadian function. Using transgenic mice that over-express androgen receptor (AR) only in neurons, the current study investigated the influence of neural AR on the function of the SCN. In particular, it addressed the effects of androgens on circadian behaviours as well as physiological responses to light within the SCN by measuring Fos response after a phase-shifting light pulse. It was found that transgenic mice demonstrate a smaller increase in Fos expression in response to a light pulse than do wildtypes. Interpretations of our findings, including the possible functional significance of AR within the SCN, are discussed.

Normal breast growth and development depends on functional androgen:estrogen (A:E) balance. Androgen actions are mediated by the androgen receptor (AR), a DNA-binding, transcriptional-regulatory protein. Decreased AR transactivational. activity lowers A:E balance and may result in functional hyperestrogenicity: this could promote the pathogenesis of breast cancer (BC). The present study is the first to seek AR mutations in female BC. The length of the polymorphic CAG-repeat in exon 1 of the AR correlates inversely with the transactivational activity of the AR. Using 10% polyacrylamide gels, I found a significant (p < 0.0001) shift to greater CAG-repeat lengths in BC samples. This suggests a role for ARs with long polyglutamine tracts in the initiation and/or progression of BC. Exons 2--8 of the AR in 81 fresh frozen BC tumor tissues were screened for mutations using SSCP analysis. I did not detect any mutations in these exons.

No description available.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock that is critical in the temporal organization of circadian activity. The SCN coordinates the rhythmic secretion of gonadal hormones, and in turn, reproductive hormones may act on their receptors within the SCN to alter circadian function. Using transgenic mice that over-express androgen receptor (AR) only in neurons, the current study investigated the influence of neural AR on the function of the SCN. In particular, it addressed the effects of androgens on circadian behaviours as well as physiological responses to light within the SCN by measuring Fos response after a phase-shifting light pulse. It was found that transgenic mice demonstrate a smaller increase in Fos expression in response to a light pulse than do wildtypes. Interpretations of our findings, including the possible functional significance of AR within the SCN, are discussed.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 4 uppsatser.

Thesis (Ph. D.)--Ohio State University, 2008.

Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 114-131). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--Lehigh University, 2000. / Includes bibliographical references and vita.

In two experiments, immature female Sprague-Dawley rats treated with superovulatory doses of pregnant mare serum gonadotropin (PMSG) were used to study the effects of antiandrogen, hydroxyflutamide, on steroid production, particularly the biologically active androgens, testosterone, 5α-dihydrotestosterone, and androstenedione. In the first experiment, the animals were given either 5 mg hydroxyflutamide or vehicle alone at 30 and 36 h following 40 IU PMSG. Compared to the vehicle group, hydroxyflutamide treatment significantly reduced the percentage of degenerate oocytes recovered from oviducts (p<0.05). Serum levels of aromatizable androgens, testosterone and androstenedione, and their aromatized product, estradiol-17ß significantly decreased (p<0.05) in hydroxyflutamide-treated group; however, the serum concentrations of nonaromatizable androgen, 5α-dihydrotestosterone, was not statistically different between the two groups. In the second experiment, ovaries stimulated with 4 or 40 IU PMSG were obtained 48 h later and cultured in the presence and absence of hydroxyflutamide (10⁻⁵M) and/or testosterone (10⁻⁷ M) to study [4⁻¹⁴C] pregnenolone metabolism to major steroids. In 40 IU stimulated ovaries, hydroxyflutamide significantly decreased the metabolism of pregnenolone to progesterone (p<0.01) and androstenedione (p<0.01) while the production of estradiol-17ß increased significantly (p<0.05); however, pregnenolone conversions to testosterone and 5α-dihydrotestosterone were not statistically different between the untreated and hydroxyflutamide-treated cultures. Testosterone completely reversed the hydroxyflutamide-induced alteration of pregnenolone metabolism. In contrast, there was no difference in the pregnenolone conversion patterns between the untreated and hydroxyflutamide or hydroxyflutamide plus testosterone groups in the culture of ovaries stimulated with 4 IU PMSG. Present results confirm previous reports that antiandrogen, hydroxyflutamide, decreases the percentage of abnormal oocytes recovered from superovulating rats, and indicates that this hydroxyflutamide effect may be partly mediated by altered ovarian steroidogenesis, specifically the reduced hypersecretion of aromatizable androgens, testosterone and androstenedione, and/or estradiol-17ß. / Medicine, Faculty of / Obstetrics and Gynaecology, Department of / Graduate

No description available.