Effects of progesterone and RU486 on the development and expression of adult male sexual behaviour and gene expression in the amygdala and preoptic area of the hypothalamus
A. B. Breton A , K. J. Austin A , M. G. Leedy B C and B. M. Alexander A DA Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA.
B Department of Social Work, University of Wyoming, Laramie, WY 82071, USA.
C Present address: Department of Social Work, Appalachian State University, Boone, NC 28605, USA.
D Corresponding author. Email: balex@uwyo.edu
Reproduction, Fertility and Development 24(7) 916-922 https://doi.org/10.1071/RD12006
Submitted: 5 January 2012 Accepted: 9 February 2012 Published: 14 March 2012
Abstract
The number of progesterone receptors is greater in the male than female neonatal rat hypothalamus. The aims of the present study were to determine developmental effects of progesterone on the expression of adult male sexual behaviour and whether changes in behaviour were reflected by altered gene expression within the hypothalamic preoptic area (POA) or medial amygdala. Male rats were treated with progesterone (40 µg kg–1, i.p.), the progesterone receptor antagonist RU486 (40 µg kg–1, i.p.) or an equal volume of vehicle (10% ethanol, 90% corn oil) on postnatal Days 1–5. Treatment with either progesterone or RU486 inhibited (P ≤ 0.07) the initial expression of consummatory sexual behaviour at 10.5 weeks of age without influencing growth or serum concentrations of testosterone. Sexual interest, as measured by latency to exhibiting mounting behaviour or the number of mounts achieved, was not influenced by treatment with either progesterone or RU486. The effects of treatment with progesterone or RU486 on sexual behaviour were diminished by experience. Microarray analysis of the POA indicated 61 genes that were upregulated and 49 that were downregulated (P ≤ 0.01) following RU486 treatment of male rats. However, the altered expression of selected genes was not confirmed by real-time reverse transcription–polymerase chain reaction. The expression of targeted genes within the amygdala was not influenced by treatment with either progesterone or RU486. Neonatal treatment with RU486, but not progesterone, decreased testes weight (P = 0.02) without affecting testes morphology. The results indicate that altering the progesterone environment during a critical developmental period affects the expression of behaviour, but that changes in behaviour are not mirrored by the altered expression of selected genes.
Additional keyword: testes.
References
Bhusari, S., Liu, Z., Hearne, L. B., Spiers, D. E., Lamberson, W. R., and Antoniou, E. (2007). Expression profiling of heat stress effects on mice fed ergot alkaloids. Toxicol. Sci. 95, 89–97.| Expression profiling of heat stress effects on mice fed ergot alkaloids.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtlChtLbF&md5=3224b5f649b64a09f9ee5a6fd9af9162CAS | 17093207PubMed |
Cammack, K. M., Antoniou, E., Hearne, L., and Lamberson, W. R. (2009). Testicular gene expression in male mice divergent for fertility after heat stress. Theriogenology 71, 651–661.
| Testicular gene expression in male mice divergent for fertility after heat stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFSmtL4%3D&md5=f808992941ae98b3cae37b0114e912c5CAS | 18992933PubMed |
Dwyer, C. M., and Smith, L. A. (2008). Parity effects on maternal behavior are not related to circulating oestradiol concentrations in two breeds of sheep. Physiol. Behav. 93, 148–154.
| Parity effects on maternal behavior are not related to circulating oestradiol concentrations in two breeds of sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlsVSlsQ%3D%3D&md5=ae850a461b80138147b8791c90ace04dCAS | 17884115PubMed |
Hull, E. M. (1981). Effects of neonatal exposure to progesterone on sexual behavior of male and female rats. Physiol. Behav. 26, 401–405.
| Effects of neonatal exposure to progesterone on sexual behavior of male and female rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3MXhsFCju7k%3D&md5=c8f01d8a4f5049afea97745bae2ab3faCAS | 7243957PubMed |
Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method. Methods 25, 402–408.
| Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFelt7s%3D&md5=c02316d2aa02af4c464251269a77c9c9CAS | 11846609PubMed |
Lonstein, J. S., Quadros, P. S., and Wagner, C. K. (2001). Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats. Behav. Neurosci. 115, 58–70.
| Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjt1SrtL8%3D&md5=5d2534519c63471e00fecd941c303ad0CAS | 11256453PubMed |
Naoki, T., Ikuya, S., Osamu, T., and Keishi, M. (1988). RU486, a progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and reverses the growth inhibition by progestins. J. Steroid Biochem. 31, 161–166.
| RU486, a progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and reverses the growth inhibition by progestins.Crossref | GoogleScholarGoogle Scholar |
Oettel, M., and Mukhopadhyay, A. K. (2004). Progesterone: the forgotten hormone in men? Aging Male 7, 236–257.
| Progesterone: the forgotten hormone in men?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXps1yktbw%3D&md5=4a3425653a03e513dfd0b7f9223609adCAS | 15669543PubMed |
Quadros, P. S., Lopez, V., DeVries, G. J., Chung, W. C. J., and Wagner, C. K. (2002). Progesterone receptors and the sexual differentiation of the medial preoptic nucleus. J. Neurobiol. 51, 24–32.
| Progesterone receptors and the sexual differentiation of the medial preoptic nucleus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XivV2ktL4%3D&md5=9b7f78fe537c3ccf985841407902e457CAS | 11920725PubMed |
Rhoda, J., Valens, M., Edwards, D. A., and Roffi, J. (1987). Effect of progesterone on the testosterone and estradiol levels in the hypothalamus of neonatal rats. Biol. Neonate 51, 255–259.
| Effect of progesterone on the testosterone and estradiol levels in the hypothalamus of neonatal rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXitVOrurc%3D&md5=d8b634119d1857869f960a0a07aa91d4CAS | 3593806PubMed |
Rozen, S., and Skaletsky, H. (2000). Primer3 on the WWW for general users and for biologist programmers. Methods Mol. Biol. 132, 365–386.
| 1:CAS:528:DyaK1MXmslKqsbo%3D&md5=f49f8151abf9cb9f0cf1067a703936c9CAS | 10547847PubMed |
Sanchez, P. E., Ryan, M. A., Kridelka, F., Gielen, I., Ren, S. G., Albertson, B., Malozowski, S., Nieman, L., and Cassorla, F. (1989). RU-486 inhibits rat gonadal steroidogenesis. Horm. Metab. Res. 21, 369–371.
| RU-486 inhibits rat gonadal steroidogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXlvVOktrY%3D&md5=4aa6718c8cc9b8b737f395520eb042e7CAS | 2789168PubMed |
Schneider, J. S., Burgess, C., Sleiter, N. C., DonCarlos, L. L., Lydon, J. P., O’Malley, B., and Levine, J. E. (2005). Enhanced sexual behaviors and androgen receptor immunoreactivity in the male progesterone receptor knockout mouse. Endocrinology 146, 4340–4348.
| Enhanced sexual behaviors and androgen receptor immunoreactivity in the male progesterone receptor knockout mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtVGmurbI&md5=e182b29b56b150c77605b07515eb5d4aCAS | 16002522PubMed |
Streit, S., Michalski, C. W., Erkan, M., Friess, H., and Kleeff, J. (2009). Confirmation of DNA microarray-derived differentially expressed genes in pancreatic cancer using quantitative RT-PCR. Pancreatology 9, 577–582.
| Confirmation of DNA microarray-derived differentially expressed genes in pancreatic cancer using quantitative RT-PCR.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFWrs77N&md5=e1cc83ba139e49ac0eb7e7bdbdaf7cf0CAS | 19657213PubMed |
van der Schoot, P., and Baumgarten, R. (1990). Effects of treatment of male and female rats in infancy with mifepristone on reproductive function in adulthood. J. Reprod. Fertil. 90, 255–266.
| Effects of treatment of male and female rats in infancy with mifepristone on reproductive function in adulthood.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXjs1WmtA%3D%3D&md5=f5fae2aa742d636ca5d49ab3f6ed1e2cCAS | 2121971PubMed |
Wagner, C. K. (2008). Minireview: progesterone receptors and neural development: a gap between bench and bedside? Endocrinology 149, 2743–2749.
| Minireview: progesterone receptors and neural development: a gap between bench and bedside?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXms1entrw%3D&md5=e18c235c1b123c27ae28958cbecb630fCAS | 18308849PubMed |
Wagner, C. K., Nakayama, A. Y., and De Vries, G. J. (1998). Potential role of maternal progesterone in the sexual differentiation of the brain. Endocrinology 139, 3658–3661.
| Potential role of maternal progesterone in the sexual differentiation of the brain.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXkvVKht7c%3D&md5=d6dcb200228c208870cdd376f0cbf3adCAS | 9681521PubMed |
Wehle, H., Moll, J., and Cato, A. C. B. (1995). Molecular identification of steroid analogs with dissociated antiprogestin activities. Steroids 60, 368–374.
| Molecular identification of steroid analogs with dissociated antiprogestin activities.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXlvV2jt7c%3D&md5=93df3244303040672a465143cd55743aCAS | 7570709PubMed |
Weisz, J., and Ward, I. L. (1980). Plasma testosterone and progesterone titers of pregnant rats, their male and female fetuses, and neonatal offspring. Endocrinology 106, 306–316.
| Plasma testosterone and progesterone titers of pregnant rats, their male and female fetuses, and neonatal offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3cXntlChsw%3D%3D&md5=4ff7ba738b6c72d1539ec12b257f3346CAS | 7349961PubMed |
