Androgen Therapy Reverses Injuries Caused By Ethanol Consumption In The Prostate: Testosterone As A Possible Target To Ethanol-related Disorders

Aims: Chronic ethanol consumption leads to reproductive damages, since it can act directly in the tissues or indirectly, causing a hormonal imbalance. Prostate is a hormone-dependent gland and, consequently, susceptible to ethanol. The potential of testosterone therapy in the ethanol-related disorders was investigated in the prostate microenvironment. Main methods: UChB rats aged 90 dayswere divided into 2 experimental groups (n = 20): C: drinking water only and EtOH: drinking 10% (v/v) ethanol at > 2 g/kg body weight / day + water. At 150 days old, 10 rats from each group received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks, constituting T and EtOH+T, while the remaining animals received corn oil as vehicle. Animals were euthanized at 180 days old, by decapitation. Blood was collected to obtain hormone concentrations and ventral prostate was dissected and processed for light microscope and molecular analyses. Key findings: Ventral prostateweight, plasma testosterone and DHT and intraprostatic testosterone concentrations were increased after testosterone treatment. Plasma estradiol level was reduced in the EtOH+T. Inflammatory foci, metaplasia and epithelial atrophy were constantly found in the prostate of EtOH and were not observed after hormonal therapy. No differences were found in the expression of AR, ERβ and DACH-1. Additionally, testosterone treatment down-regulated ERα and increased the e-cadherin and α-actinin immunoreactivities. Significance: Testosterone was able to reverse damages caused by ethanol consumption in the prostate microenvironment and becomes a possible target to be investigated to ethanol-related disorders.1202230Adams, J.Y., Leav, I., Lau, K.M., Ho, S.M., Pflueger, S.M., Expression of estrogen receptor beta in the fetal, neonatal, and prepubertal human prostate (2002) Prostate, 52, pp. 69-81Bosland, M.C., Sex steroids and prostate carcinogenesis: Integrated, multifactorial working hypothesis (2006) Ann. N. Y. Acad. Sci., 1089, pp. 168-176Campana, A.O., Burini, R.C., Outa, A.Y., Camargo, J.L., Experimental protein deficiency in adult rats (1975) Rev. Bras. Pesqui. Med. Biol., 8, pp. 221-226Cândido, E.M., Carvalho, C.A.F., Martinez, F.E., Cagnon, V.H.A., Experimental alcoholism and pathogenesis of prostatic diseases in UChB rats (2007) Cell Biol. Int., 31, pp. 459-472Carreau, S., Bourguiba, S., Lambard, S., Galeraud-Denis, I., Genissel, C., Levallet, J., Reproductive system: Aromatase and estrogens (2003) Mol. Cell. Endocrinol., 193, pp. 137-143Cordeiro, R.S., Scarano, W.R., Campos, S.G., Santos, F.C., Vilamaior, P.S., Góes, R.M., Taboga, S.R., Androgen receptor in the Mongolian gerbil ventral prostate: Evaluation during different phases of postnatal development and following and androgen blockage (2008) Micron, 39, pp. 1312-1324Debes, J.D., Tindall, D.J., The role of androgens and the androgen receptor in prostate cancer (2002) Cancer Lett., 187, pp. 1-7Ellem, S.J., Risbrindger, G.P., The dual, opposing roles of estrogen in the prostate (2009) Ann. N. Y. Acad. Sci., 1155, pp. 174-186Fávaro, W.J., Cagnon, V.H.A., Immunolocalization of androgen and oestrogen receptors in the ventral lobe of rat (Rattus norvegicus) prostate after long-term treatment with ethanol and nicotine (2008) Int. J. Androl., 31, pp. 609-618García-Cao, I., Duran, A., Collado, M., Carrascosa, M.J., Martín-Caballero, J., Flores, J.M., Tumor suppression activity of the proapoptotic regulator PAR4 (2005) EMBO Rep., 6, pp. 577-583Gomes, I.C., Cagnon, V.H.A., De Luca, I.M., Stereology and ultrastructure of the seminal vesicle of C57/BL/6J mice following chronic alcohol ingestion (2002) Tissue Cell, 34, pp. 177-186Gonc¸avez, B.F., Campos, S.G.P., Zanetoni, C., Scarano, W.R., Faleiros, L.R., Jr., Amorim, R.L., Góes, R.M., Taboga, S.R., A new proposed rodent model of chemically induced prostate carcinogenesis: Distinct time-course prostate cancer progression in the dorsolateral and ventral lobes (2013) Prostate, 73, pp. 1202-1213Griffts, K., Morton, M.S., Nicholson, R.I., Androgens, androgens receptors, antiandrogens and the treatment of prostate cancer (1997) Eur. Urol., 32, pp. 24-40Guess, H.A., Benign prostatic hyperplasia and prostate cancer (2001) Epidemiol. Rev., 23, pp. 152-158Gurumurthy, S., Rangnekar, V.M., Par-4 inducible apoptosis in prostate cancer cells (2004) J. Cell. Biochem., 91, pp. 504-512Harkonen, P.L., Makela, S.I., Role of estrogens in development of prostate cancer (2004) J. Steroid Biochem. Mol. Biol., 92, pp. 297-305Kawashima, H., Nakatani, T., Involvement of estrogen receptors in prostatic diseases (2012) Int. J. Urol., 19, pp. 512-522Landau, D., Tsakok, T., Aylwin, S., Hughes, S., Should testosterone replacement be offered to hypogonadal men treated previously for prostatic carcinoma? (2012) Clin. Endocrinol., 76, pp. 179-181Lewis, M.I., Horvitz, G.D., Clemmons, D.R., Fournier, M., Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone (2002) Am. J. Physiol. Endocrinol. Metab., 282, pp. 483-490Li, T.K., Lumeng, L., McBride, W.J., Murphy, J.M., Rodent lines selected for factors affecting alcohol solution (1987) Alcohol Alcohol., 1, pp. 91-96Lieber, C.S., Alcohol and the liver: 1984 update (1984) Hepatology, 4, pp. 1243-1260Lin, E.Y., Pollard, J.W., Role of infiltrated leucocytes in tumour growth and spread (2004) Br. J. Cancer, 90, pp. 2053-2058Mardones, J., Segovia-Riquelme, N., Thirty two years of selection of rats by ethanol preference: UChA and UChB strains (1983) Neurobehav. Toxicol. Teratol., 5, pp. 171-178Morani, A., Warner, M., Gustafsson, J.A., Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues (2008) J. Intern. Med., 264, pp. 128-142Muthusamy, S., Andersson, S., Kim, H.J., Butler, R., Waage, L., Bergerheim, U., Estrogen receptor beta and 17beta-hydroxysteroid dehydrogenase type 6, a growth regulatory pathway that is lost in prostate cancer (2011) Proc. Natl. Acad. Sci. U. S. A., 108, pp. 20090-20094National Research of Council, (1995) Nutrient Requirements of Laboratory Animals, 4th Ed., , National Academy Press, Washington, DCRittmaster, R.S., 5α-Reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction (2008) Best Pract. Res. Clin. Endocrinol. Metab., 22, pp. 389-402Rochel-Maia, S.S., Santos, F.C.A., Alonso-Magdalena, P., Góes, R.M., Vilamaior, P.S.L., Warner, M., Estrogen receptors alpha and beta in male and female gerbil prostates (2013) Biol. Reprod., 88, pp. 1-7Ronis, M.J.J., Wands, J.R., Badger, T.M., De La Monte, S.M., Lang, C.H., Calissendorff, J., Alcohol-induced disruption of endocrine signaling (2007) Alcohol. Clin. Exp. Res., 31, pp. 1269-1285Roy-Burman, P., Wu, H., Powell, W.C., Hagenkord, J., Cohen, M.B., Genetically defined mouse models that mimic natural aspects of human prostate cancer development (2004) Endocr. Relat. Cancer, 11, pp. 225-254Salomen, I., Huhtaniemi, I., Effects of chronic ethanol diet on pituitary-testicular function of the rat (1990) Biol. Reprod., 42, pp. 55-62Sáttolo, S., Carvalho, C.A.F., Cagnon, V.H.A., Influence of hormonal replacement on the ventral lobe of the prostate of rats (Rattus novergicus albinus) submitted to chronic ethanol treatment (2004) Tissue Cell, 36, pp. 417-430Saxena, S., Meehan, D., Coney, P., Wimalasena, J., Ethanol has direct inhibitory effects on steroidogenesis in human granulosa cells: Specific inhibition of LH action (1990) Alcohol. Clin. Exp. Res., 14, pp. 522-527Scarano, W.R., Vilamaior, P.S.L., Taboga, S.R., Tissue evidence of the testosterone role on the abnormal growth and aging effects reversion in the gerbil (Meriones unguilatus) prostate (2006) Anat. Rec. A Discov. Mol. Cell Biol., 11, pp. 1190-1200Sugiyama, N., Barros, R.P., Warner, M., Gustafsson, J.A., ERβ: Recent understanding of estrogen signaling (2010) Trends Endocrinol. Metab., 21, pp. 545-552Tadic, S.D., Elm, M.S., Subbotin, V.M., Eaggon, P.K., Hypogonadism precedes liver feminization in chronic alcohol-fed male rats (2000) Hepatology, 31, pp. 1135-1140Thomas, C., Gustafsson, J.A., The different roles of ER subtypes in cancer biology and therapy (2011) Nat. Rev., 11, pp. 597-608Weihua, Z., Warner, M., Gustafsson, J.A., Estrogen receptor beta in the prostate (2002) Mol. Cell. Endocrinol., 193, pp. 1-5Weibel, E.R., Principles and methods for the morphometric study of the lung and other organs (1963) Lab. Investig., 12, pp. 131-155Wilson, J., Balkwill, F., The role of cytokines in the epithelial cancer microenvironment (2002) Semin. Cancer Biol., 12, pp. 113-120Wu, K., Katiyar, S., Witkiewicz, A., Li, A., McCue, P., Song, L.N., The cell fate determination factor dachshund inhibits androgen receptor signaling and prostate cancer cellular growth (2009) Cancer Res., pp. 593347-593355Yatkin, E., Bernoulli, J., Talvitie, E., Santti, R., Inflammation and epithelial alterations in the rat prostate: Impact of the androgen to oestrogen ratio (2009) Int. J. Androl., 32, pp. 399-41

Variations In Maternal Care Alter Corticosterone And 17beta-estradiol Levels, Estrous Cycle And Folliculogenesis And Stimulate The Expression Of Estrogen Receptors Alpha And Beta In The Ovaries Of Uch Rats

Background: Variations in maternal care are associated with neonatal stress, hormonal disturbances and reproductive injuries during adulthood. However, the effects of these variations on sex hormones and steroid receptors during ovary development remain undetermined. This study aimed to investigate whether variations in maternal care are able to influence the hormonal profile, follicular dynamics and expression of AR, ER-alpha and ER-beta in the ovaries of UCh rat offspring.Methods: Twenty-four adult UCh rats, aged 120 days, were randomly divided into two groups (UChA and UChB) and mated. Maternal care was assessed from birth (day 0) to the 10th postnatal day (PND). In adulthood, twenty adult female rats (UChA and UChB offspring; n = 10/group), aged 120 days, were euthanized by decapitation during the morning estrus.Results: UChA females (providing high maternal care) more frequently displayed the behaviors of carrying pups, as well as licking/grooming and arched back nursing cares. Also, mothers providing high care had elevated corticosterone levels. Additionally, offspring receiving low maternal care showed the highest estrous cycle duration, increased corticosterone and 17beta-estradiol levels, overexpression of receptors ER-alpha and ER-beta, increased numbers of primordial, antral and mature follicles and accentuated granulosa cell proliferation.Conclusions: Our study suggests that low maternal care alters corticosterone and 17beta-estradiol levels, disrupting the estrous cycle and folliculogenesis and differentially regulating the expression of ER-alpha and ER-beta in the ovaries of adult rats. © 2011 Amorim et al; licensee BioMed Central Ltd.9Walker, C.D., Deschamps, S., Proulx, K., Tu, M., Salzman, C., Woodside, B., Lupien, S., Richard, D., Mother to infant or infant to mother? Reciprocal regulation of responsiveness to stress in rodents and the implications for humans (2004) J Psychiatry Neurosci, 29, pp. 364-382. , 518866, 15486606Liu, D., Dioro, J., Tannenbaum, B., Caldji, C., Francis, D., Freedman, A., Shaema, S., Meaney, M.J., Maternal care, hipocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal response to stress (1997) Science, 277, pp. 1659-1662. , 10.1126/science.277.5332.1659, 9287218Francis, D.D., Diorio, J., Plotsky, P.M., Meaney, M.J., Environmental enrichment reverses the effects of maternal separation on stress reactivity (2002) J Neurosci, 22, pp. 7840-7843Jaworski, J.N., Francis, D.D., Brommer, C.L., Morgan, E.T., Kuhar, M.J., Effects of early maternal separation on ethanol intake, GABA receptor and metabolizing enzymes in adult rats (2005) Psychopharmacology, 181, pp. 8-15. , 10.1007/s00213-005-2232-4, 15830234Uriarte, R., Breigeiron, M.K., Benetti, F., Rosa, X.F., Lucion, A.B., Effects of maternal care on the development, emotionality, and reproductive function in male and female rats (2007) Dev Psychobiol, 49, pp. 451-462. , 10.1002/dev.20241, 17577226Champagne, F.A., Meaney, M.J., Transgenerational effects of social environment on variations in maternal care and behavioral response to novelty (2007) Behav Neurosci, 121, pp. 1353-1363Champagne, F.A., Francis, D.D., Mar, A., Meaney, M.J., Variations in maternal care in the rat as a mediating influence for the effects of environment on development (2003) Physiol Behav, 79, pp. 359-371. , 10.1016/S0031-9384(03)00149-5, 12954431Numan, M., Maternal Behavior (1994), pp. 221-302. , The Physiology of Reproduction Raven Press (New York), Knobil E, Neill, JD, 2Macrí, S., Mason, G., Wurbel, H., Dissociation in the effects of neonatal maternal separations on maternal care and the offspring's HPA and fear responses in rats (2004) Eur J Neurosci, 20, pp. 1017-1024. , 10.1111/j.1460-9568.2004.03541.x, 15305870Petersen, C.A., Boccia, M.L., Oxytocin antagonism alters rat dams' oral grooming and upright posturing over pups (2003) Physiol Behav, 80, pp. 233-241. , 10.1016/j.physbeh.2003.07.011, 14637221Catalani, A., Alemà, G.S., Cinque, C., Zuena, A.R., Casolini, P., Maternal corticosterone effects on hypothalamus-pituitary-adrenal axis regulation and behavior of the offspring in rodents (2011) Neurosci Biobehav Rev, 35, pp. 1502-1517. , 10.1016/j.neubiorev.2010.10.017, 21056056Michel, G.F., Tyler, A.N., Can Knowledge of developmental processes illuminate the evolution of parental care? (2007) Dev Psychobiol, 49, pp. 33-44. , 10.1002/dev.20195, 17186511Stern, J.M., Johnson, S.K., Ventral somatosensory determinants of nursing care in Norway rats. Effects of variations in quality and quality of pup's stimuli (1990) Physiol Behav, 47, pp. 993-1011. , 10.1016/0031-9384(90)90026-Z, 2388953Rosenblatt, J.S., Siegel, H.I., Mayer, A.D., Progress in the study of maternal behavior in the rat: hormonal, nonhormonal, sensory, and developmental aspects (1979), 10, pp. 225-311. , Advances in the study of care, Acad. Press, New York, Rosenblatt JS, Hinde RA, Beer C, Busnel MCRosenblatt, J.S., Hormonal and nonhormonal regulation of maternal behavior: A theoretical survey (1980) Reprod Nutr Dev, 20, pp. 791-800. , 10.1051/rnd:19800505, 6818633Polan, H.J., Hofer, M.A., Maternally directed orienting behaviors of newborn rats (1999) Dev Psychobiol, 34, pp. 269-279. , 10.1002/(SICI)1098-2302(199905)34:23.0.CO;2-L, 10331151Coutellier, L., Friedrich, A., Failing, K., Wurbel, H., Variations in the postnatal environment in mice: Effects on maternal behaviour and behavioural and endocrine responses in the adult offspring (2008) Physiol Behav, 93, pp. 395-407. , 10.1016/j.physbeh.2007.09.008, 17961613Auger, A.P., Ligand-independent activation of progestin receptors: relevance for female sexual care (2001) Reproduction, 122, pp. 847-855. , 10.1530/rep.0.1220847, 11732980Koike, S., Nii, A., Sakai, M., Muramatsu, M., The steroid binding domain of porcine estrogen receptor (1987) Biochemistry, 5, pp. 2563-2568Kuiper, G.G., Enmark, E., Pelto-Huikko, M., Nilsson, S., Gustafsson, J.A., Cloning of a novel receptor expressed in rat prostate and ovary (1996) Proc Natl Acad Sci USA, 11, pp. 5925-5930Champagne, F.A., Weaver, I.C.G., Diorio, J., Sharma, S., Meaney, M.J., Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area (2003) Endocrinology, 144, pp. 4720-4724. , 10.1210/en.2003-0564, 12959970Erskine, M.S., Lehmann, M.L., Cameron, N.M., Polston, E.K., Co-regulation of female sexual behavior and pregnancy induction: an exploratory synthesis (2004) Behav Brain Res, 153, pp. 295-315. , 10.1016/j.bbr.2004.01.026, 15265625Cameron, N., Del Corpo, A., Diorio, J., McAllister, K., Sharma, S., Meaney, M.J., Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat (2008) PLoS One, 21, pp. e2210Levine, J.E., Chappell, L.M., Bauer-Dantoin, A.C., Besecke, L.M., Conaghan, L.A., Legan, S.J., Meredith, J.M., Wolfe, A.M., Neuroendocrine regulation of luteinizing hormone pulse generator in the rat (1991) Recent Prog Horm Res, 47, pp. 97-153Herbison, A.E., Multimodal influence of estrogen upon gonadotropin releasing hormone neurons (1998) Endocrinol Rev, 19, pp. 302-330Mahesh, V.B., Brann, D.W., Regulation of the preovulatory gonadotropin surge by endogenous steroids (1998) Steroids, 63, pp. 616-629. , 10.1016/S0039-128X(98)00075-0, 9870258Mardones, J., Segovia-Riquelme, N., Thirty-two years of selection of rats by ethanol preference: UChA and UChB strains (1983) Neurobehav Toxicol Teratol, 5, pp. 171-178Rosenblatt, J.S., Nonhormonal basis of maternal behavior in the rat (1967) Science, 16, pp. 1512-1514Fleming, A.S., Rosenblatt, J.S., Maternal behavior in the virgin and lactating rat (1974) J Comp Physiol Psychol, 86, pp. 957-972Myers, M.M., Brunelli, S.A., Squire, J.M., Shindeldecker, R.D., Hofer, M.A., Maternal behavior of SHR rats and its relationship to offspring blood pressures (1989) Dev Psychobiol, 22, pp. 29-53. , 10.1002/dev.420220104, 2912812Pryce, C.R., Bettschen, D., Feldon, J., Comparison of the effects of early handling and early deprivation on maternal care in the rat (2001) Dev Psychobiol, 38, pp. 239-251. , 10.1002/dev.1018, 11319730Marcondes, F.K., Bianchi, F.J., Tanno, A.P., Determination of the estrous cycle phases of rats: some helpful considerations (2002) Braz J Biol, 62, pp. 609-614. , 10.1590/S1519-69842002000400008, 12659010Plowchalk, D.R., Smith, B.J., Mattison, D.R., Assessment of toxicity to the ovary using follicle quantitation and morphometrics (1993) Methods Toxicol, 3, pp. 57-68Cameron, N.M., Champagne, F.A., Parent, C., Fish, E.W., Ozaki-Kuroda, K., Meaney, M.J., The programming of individual differences in defensive responses and reproductive strategies in the rat through variations in maternal care (2005) Neurosci Biobehav Rev, 29, pp. 843-865. , 10.1016/j.neubiorev.2005.03.022, 15893378Cameron, N.M., Fish, E.W., Meaney, M.J., Maternal influences on the sexual behavior and reproductive success of the female rat (2008) Horm Behav, 54, pp. 178-184. , 10.1016/j.yhbeh.2008.02.013, 18417127Cameron, N.M., Soehngen, E., Meaney, M.J., Variation in maternal care influences ventromedial hypothalamus activation in the rat (2011) J Neuroendocrinol, 23, pp. 393-400. , 10.1111/j.1365-2826.2011.02124.x, 21418337Caldji, C., Tannenbaum, B., Sharm, S., Francis, D., Plotsky, P.M., Meaney, M.J., Maternal care during infancy regulates the development of neural systems mediating the expression of fearfulness in the rat (1998) Proc Natl Acad Sci USA, 95, pp. 5335-5340. , 10.1073/pnas.95.9.5335, 20261, 9560276Meaney, M.J., Szyf, M., Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome (2005) Dialogues Clin Neurosci, 7, pp. 103-123. , 3181727, 16262207Rosenblatt, J.S., Mayer, A.D., Giordano, A.L., Hormonal basis during pregnancy for the onset of maternal behaviour in the rat (1988) Psychoneuroendocrinology, 13, pp. 29-46. , 10.1016/0306-4530(88)90005-4, 2967517Casolini, P., Domenici, M.R., Cinque, C., Alema, G.S., Chiodi, V., Galluzzo, M., Musumeci, M., Catalani, A., Maternal exposure to low levels of corticosterone during lactation protects the adult offspring against ischemic brain damage (2007) J Neurosci, 27, pp. 7041-7046. , 10.1523/JNEUROSCI.1074-07.2007, 17596453Graham, M.D., Rees, S.L., Steiner, M., Fleming, A.S., The effects of adrenalectomy and corticosterone replacement on maternal memory in postpartum rats (2006) Horm Behav, 49, pp. 353-361. , 10.1016/j.yhbeh.2005.08.014, 16300764Catalani, A., Casolini, P., Scaccianoce, S., Patacchioli, F.R., Spinozzi, P., Angelucci, L., Maternal corticosterone during lactation permanently affects brain corticosteroid receptors, stress response and behaviour in rat progeny (2000) Neuroscience, 100, pp. 319-325. , 10.1016/S0306-4522(00)00277-3, 11008169Leret, M.L., Peinado, V., Suarez, L.M., Tecedor, L., Gamallo, A., Gonzalez, J.C., Role of maternal adrenal glands on the developing serotoninergic and aminoacidergic systems of the postnatal rat brain (2004) Int J Dev Neurosci, 22, pp. 87-93. , 10.1016/j.ijdevneu.2003.12.005, 15036383Wilcoxon, J.S., Redei, E.E., Maternal glucocorticoid deficit affects hypothalamic-pituitary-adrenal function and behavior of rat offspring (2007) Horm Behav, 51, pp. 321-327. , 10.1016/j.yhbeh.2006.11.006, 1865577, 17275820Lalmansingh, A.S., Uht, R.M., Estradiol regulates corticotropin-releasing hormone gene (crh) expression in a rapid and phasic manner that parallels estrogen receptor-alpha and -beta recruitment to a 3',5'-cyclic adenosine 5'-monophosphate regulatory region of the proximal crh promoter (2008) Endocrinology, 149, pp. 346-357. , 2194609, 17947358Miller, W.J., Suzuki, S., Miller, L.K., Handa, R., Uht, R.M., Estrogen receptor (ER) beta isoforms rather than ERalpha regulate corticotropin-releasing hormone promoter activity through an alternate pathway (2004) J Neurosci, 24, pp. 10628-10635. , 10.1523/JNEUROSCI.5540-03.2004, 15564578Yen, S.S.C., Lein, A., The apparent paradox of the negative and positive feedback control system on gonadotropin secretion (1976) Am J Obstet Gynecol, 126, pp. 942-954Shivers, B.D., Harlan, R.E., Morrell, J.I., Pfaff, D.W., Absence of estradiol concentration in cell nuclei of LHRH-immunoreactive neurons (1983) Nature, 304, pp. 345-347. , 10.1038/304345a0, 6348552Zhao, L., Watanabe, M., Yano, T., Yanagisawa, J., Nakagawa, S., Oishi, H., Wada-Hiraike, O., Taketani, Y., Analysis of the status of the novel estrogen receptor α (ERα) coactivator p72 in endometrial cancer and its cross talk with erbB-2 in the transactivation of ERα (2008) Mol Med Report, 1, pp. 387-390Pelletier, G., Labrie, C., Labrie, F., Localization of oestrogen receptor alfa, oestrogen beta receptor and androgen receptors in the rat reproductive organs (2000) J Endocrinol, 165, pp. 359-370. , 10.1677/joe.0.1650359, 10810300Champagne, F.A., Weaver, I.C.G., Diorio, J., Dymov, S., Szyf, M., Meaney, J.M., Maternal care associated with methylation of the oestrogen receptoralpha1b promoter and oestrogen receptor-alpha expression in the medial preoptic area of female offspring (2006) Endocrinology, 147, pp. 2909-2915. , 10.1210/en.2005-1119, 16513834Chuffa, L.G., Padovani, C.R., Martinez, F.E., Ovarian structure and hormonal status of the UChA and UChB adult rats in response to ethanol (2009) Maturitas, 62, pp. 21-29. , 10.1016/j.maturitas.2008.09.027, 19019587Couse, J.F., Yates, M.M., Walker, V.R., Korach, K.S., Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERα but not ERβ (2003) Mol Endocrinol, 17, pp. 1039-1053. , 10.1210/me.2002-0398, 12624116Strauss, J.F., Hsueh, A.J.W., Ovarian hormone synthesis (2001) Endocrinology, 3, pp. 2043-2052. , Philadelphia: Saunders Company, DeGroot LJ, Jameson JL, FourthLiu, J., Hu, P., Qi, X.R., Meng, F.T., Kalsbeek, A., Zhou, J.N., Acute restraint stress increases intrahypothalamic oestradiol concentrations in conjunction with increased hypothalamic oestrogen receptor β and aromatase mRNA expression in female rats (2011) J Neuroendocrinol, 23, pp. 435-443. , 10.1111/j.1365-2826.2011.02123.x, 21392135Sen, A., Hammes, S.R., Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function (2010) Mol Endocrinol, 24, pp. 1393-1403. , 10.1210/me.2010-0006, 2903904, 20501640Nielsen, M.E., Rasmussen, I.A., Kristensen, S.G., Christensen, S.T., MØllgard, K., Wreford Andersen, E., Byskov, A.G., Yding Andersen, C., In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA (2011) Mol Hum Reprod, 17, pp. 63-70. , 10.1093/molehr/gaq073, 20843821Weil, S.J., Vendola, K., Zhou, J., Adesanya, O.O., Wang, J., Okafor, J., Bondy, C.A., Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations (1998) J Clin Endocrinol Metab, 83, pp. 2479-2485. , 10.1210/jc.83.7.2479, 9661631Kolibianakis, E.M., Papanikolaou, E.G., Fatemi, H.M., Devroey, P., Estrogen and folliculogenesis: is one necessary for the other? (2005) Curr Opin Obstet Gynecol, 17, pp. 249-253. , 10.1097/01.gco.0000169101.83342.96, 15870558Robker, R.L., Richards, J.S., Hormone-induced proliferation and differentiation of granulosa cells: A coordinated balance of the cell cycle regulators cyclin D2 and p27kip1 (1998) Mol Endocrinol, 12, pp. 924-940. , 10.1210/me.12.7.924, 9658398Brummelte, S., Galea, L.A., Chronic corticosterone during pregnancy and postpartum affects maternal care, cell proliferation and depressive-like behavior in the dam (2010) Horm Behav, 58, pp. 769-779. , 10.1016/j.yhbeh.2010.07.012, 2068807