Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-10T10:48:06.774Z Has data issue: false hasContentIssue false
  • English
  • Français

Fetal programming by androgen excess in rats affects ovarian fuel sensors and steroidogenesis

Published online by Cambridge University Press:  24 May 2019

Giselle Adriana Abruzzese Open the ORCID record for Giselle Adriana Abruzzese [Opens in a new window] ,
Maria Florencia Heber ,
Fiorella Campo Verde Arbocco ,
Silvana Rocio Ferreira  and
Alicia Beatriz Motta
Giselle Adriana Abruzzese*
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
Maria Florencia Heber
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
Fiorella Campo Verde Arbocco
Affiliation:
Laboratorio de Hormonas y Biología del Cáncer, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET, 5500 Mendoza, Argentina Laboratorio de Reproducción y Lactancia, IMBECU, Mendoza, Argentina Facultad de Ciencias Médicas, Universidad de Mendoza, Mendoza, Argentina
Silvana Rocio Ferreira
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
Alicia Beatriz Motta
Affiliation:
Laboratorio de Fisio-patología ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
*
Address for correspondence: G. A. Abruzzese, CEFYBO – CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, Sector M3, Buenos Aires, C1121 ABG, Argentina. Email: giselleabruzzese@gmail.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Fetal programming by androgen excess is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS is more than a reproductive disorder, as women with PCOS also show metabolic and other endocrine alterations. Since both ovarian and reproductive functions depend on energy balance, the alterations in metabolism may be related to reproductive alterations. The present study aimed to evaluate the effect of androgen excess during prenatal life on ovarian fuel sensors and its consequences on steroidogenesis. To this end, pregnant rats were hyperandrogenized with testosterone and the following parameters were evaluated in their female offspring: follicular development, PPARG levels, adipokines (including leptin, adiponectin, and chemerin as ovarian fuel sensors), serum gonadotropins (LH and FSH), the mRNA of their ovarian receptors, and the expression of steroidogenic mediators. At 60 days of age, the prenatally hyperandrogenized (PH) female offspring displayed both an irregular ovulatory phenotype and an anovulatory phenotype with altered follicular development and the presence of cysts. Both PH groups showed altered levels of both proteins and mRNA of PPARG and a different expression pattern of the adipokines studied. Although serum gonadotropins were not impaired, there were alterations in the mRNA levels of their ovarian receptors. The steroidogenic mediators Star, Cyp11a1, Cyp17a1, and Cyp19a1 were altered differently in each of the PH groups. We concluded that androgen excess during prenatal life leads to developmental programming effects that affect ovarian fuel sensors and steroidogenesis in a phenotype-specific way.

Keywords

Prenatal hyperandrogenismPCOSovaryPPARGadipokines
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 6 , December 2019 , pp. 645 - 658
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Chan, KA, Tsoulis, MW, Sloboda, DM. Early-life nutritional effects on the female reproductive system. J Endocrinol. 2015; 224, R45–R62.CrossRefGoogle ScholarPubMed
Franks, S. Polycystic ovary syndrome. N Engl J Med. 1995; 333, 853–861.CrossRefGoogle ScholarPubMed
Demissie, M, Lazic, M, Foecking, EM, Aird, F, Dunaif, A, Levine, JE. Transient prenatal androgen exposure produces metabolic syndrome in adult female rats. Am J Physiol Endocrinol Metab. 2008; 295, E262–E268.CrossRefGoogle ScholarPubMed
Foecking, EM, McDevitt, MA, Acosta-Martínez, M, Horton, TH, Levine, JE. Neuroendocrine consequences of androgen excess in female rodents. Horm Behav. 2008; 53, 673–692.CrossRefGoogle ScholarPubMed
Amalfi, S, Velez, LM, Heber, MF, et al. Prenatal hyperandrogenization induces metabolic and endocrine alterations which depend on the levels of testosterone exposure. PLoS One. 2012; 7, e37658.CrossRefGoogle Scholar
Ramezani Tehrani, F, Noroozzadeh, M, Zahediasl, S, Piryaei, A, Hashemi, S, Azizi, F. The time of prenatal androgen exposure affects development of polycystic ovary syndrome-like phenotype in adulthood in female rats. Int J Endocrinol Metab. 2014; 12, e16502. doi: 10.5812/ijem.16502.CrossRefGoogle ScholarPubMed
Abruzzese, GA, Heber, MF, Ferreira, SR, et al. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism. J Endocrinol. 2016; 230, 67–79.CrossRefGoogle ScholarPubMed
Abbott, DH, Barnett, DK, Levine, JE, et al. Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys1. Biol Reprod. 2008; 79, 154–163.CrossRefGoogle Scholar
Ortega, HH, Rey, F, Velazquez, MML, Padmanabhan, V. Developmental programming: effect of prenatal steroid excess on intraovarian components of insulin signaling pathway and related proteins in sheep. Biol Reprod. 2010; 82, 1065–1075.CrossRefGoogle Scholar
Torre, SD, Benedusi, V, Fontana, R, Maggi, A. Energy metabolism and fertility—a balance preserved for female health. Nat Rev Endocrinol. 2014; 10, 13–23.CrossRefGoogle Scholar
Walker, DM, Gore, AC. Transgenerational neuroendocrine disruption of reproduction. Nat Rev Endocrinol. 2011; 7, 197–207.CrossRefGoogle ScholarPubMed
Fernandez-Fernandez, R, Martini, AC, Navarro, VM, et al. Novel signals for the integration of energy balance and reproduction. Mol Cell Endocrinol. 2006; 254–255, 127–132.CrossRefGoogle ScholarPubMed
Faut, M, Elia, EM, Parborell, F, Cugnata, NM, Tesone, M, Motta, AB. Peroxisome proliferator-activated receptor gamma and early folliculogenesis during an acute hyperandrogenism condition. Fertil Steril. 2011; 95, 333–337.CrossRefGoogle ScholarPubMed
Sandoval, D, Cota, D, Seeley, RJ. The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation. Annu Rev Physiol. 2008; 70, 513–535.CrossRefGoogle ScholarPubMed
Shiue, Y-L, Chen, L-R, Tsai, C-J, Yeh, C-Y, Huang, C-T. Emerging roles of peroxisome proliferator-activated receptors in the pituitary gland in female reproduction. Biomarkers Genomic Med. 2013; 5, 1–11.CrossRefGoogle Scholar
Issemann, I, Green, S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990; 347, 645–650.CrossRefGoogle ScholarPubMed
Komar, CM. Peroxisome proliferator-activated receptors (PPARs) and ovarian function – implications for regulating steroidogenesis, differentiation, and tissue remodeling. Reprod Biol Endocrinol. 2005; 3, 41.CrossRefGoogle ScholarPubMed
Froment, P, Gizard, F, Defever, D, Staels, B, Dupont, J, Monget, P. Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition. J Endocrinol. 2006; 189, 199–209.CrossRefGoogle ScholarPubMed
Vitti, M, Di Emidio, G, Di Carlo, M, et al. Peroxisome proliferator-activated receptors in female reproduction and fertility. PPAR Res. 2016; 2016, 4612306. doi: 10.1155/2016/4612306.CrossRefGoogle ScholarPubMed
Velez, LM, Heber, MF, Ferreira, SR, Abruzzese, GA, Reynoso, RM, Motta, AB. Effect of hyperandrogenism on ovarian function. Reproduction. 2015; 149, 577–585.CrossRefGoogle ScholarPubMed
Cui, Y, Miyoshi, K, Claudio, E, et al. Loss of the Peroxisome Proliferation-Activated Receptor gamma (PPARγ) does not affect mammary development and propensity for tumor formation but leads to reduced fertility. J Biol Chem. 2002; 277, 17830–17835.CrossRefGoogle Scholar
Mitchell, M, Armstrong, DT, Robker, RL, Norman, RJ. Adipokines: implications for female fertility and obesity. Reproduction. 2005; 130, 583–597.CrossRefGoogle ScholarPubMed
Reverchon, M, Ramé, C, Bertoldo, M, Dupont, J. Adipokines and the female reproductive tract. Int J Endocrinol. 2014; 2014, 10. doi: 10.1155/2014/232454.CrossRefGoogle ScholarPubMed
Bharati, J, Bharti, MK, Kar, D, Sahoo, PR. Adipokines as metabolic modulators of ovarian functions in livestock: a mini-review. J Adv Vet Anim Res. 2016; 3, 206–213.Google Scholar
Chen, X, Jia, X, Qiao, J, Guan, Y, Kang, J. Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome. J Mol Endocrinol. 2013; 50, R21–R37.CrossRefGoogle ScholarPubMed
Muruganandan, S, Parlee, SD, Rourke, JL, Ernst, MC, Goralski, KB, Sinal, CJ. Chemerin, a Novel Peroxisome Proliferator-activated Receptor γ (PPARγ) target gene that promotes mesenchymal stem cell adipogenesis. J Biol Chem. 2011; 286, 23982–23995.CrossRefGoogle ScholarPubMed
Considine, RV. Regulation of leptin production. Rev Endocr Metab Disord. 2001; 2, 357–363.CrossRefGoogle ScholarPubMed
Dupont, J, Chabrolle, C, Ramé, C, Tosca, L, Coyral-Castel, S. Role of the peroxisome proliferator-activated receptors, adenosine monophosphate-activated kinase, and adiponectin in the ovary. PPAR Res. 2008; 2008, 176275. doi: 10.1155/2008/176275.CrossRefGoogle ScholarPubMed
Martos-Moreno, GÁ, Chowen, JA, Argente, J. Metabolic signals in human puberty: effects of over and undernutrition. Mol Cell Endocrinol. 2010; 324, 70–81.CrossRefGoogle ScholarPubMed
Elias, CF, Purohit, D. Leptin signaling and circuits in puberty and fertility. Cell Mol Life Sci. 2013; 70, 841–862.CrossRefGoogle ScholarPubMed
Karim, BO, Landolfi, JA, Christian, A, et al. Estrous cycle and ovarian changes in a rat mammary carcinogenesis model after irradiation, tamoxifen chemoprevention, and aging. Comp Med. 2003; 53, 532–538.Google Scholar
Woodruff, TK, Lyon, RJ, Hansen, SE, Rice, GC, Mather, JP. Inhibin and activin locally regulate rat ovarian folliculogenesis. Endocrinology. 1990; 127, 3196–3205.CrossRefGoogle ScholarPubMed
Paixão, L, Velez, LM, Santos, BR, et al. Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens. J Dev Orig Health Dis. 2016; 7, 384–390.CrossRefGoogle ScholarPubMed
Abramovich, D, Irusta, G, Bas, D, Cataldi, NI, Parborell, F, Tesone, M. Angiopoietins/TIE2 system and VEGF are involved in ovarian function in a DHEA rat model of polycystic ovary syndrome. Endocrinology. 2012; 153, 3446–3456.CrossRefGoogle Scholar
Livak, KJ, Schmittgen, TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001; 25, 402–408.CrossRefGoogle Scholar
Lacau de Mengido, I, Becú-Villalobos, D, Libertun, C. Sexual differences in the dopaminergic control of luteinizing hormone secretion in the developing rat. Dev Brain Res. 1987; 35, 91–95.CrossRefGoogle Scholar
Lacau-Mengido, IM, Libertun, C, Becú-Villalobos, D. Different serotonin receptor types participate in 5-hydroxytryptophan-induced gonadotropins and prolactin release in the female infantile rat. NEN. 1996; 63, 415–421.Google ScholarPubMed
Horng, S-G, Wang, T-H, Wang, H-S. Estradiol-to-testosterone ratio is associated with response to metformin treatment in women with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Chang Gung Med J. 2008; 31, 477–483.Google Scholar
Abraham, GE, Swerdloff, R, Tulchinsky, D, Odell, WD. Radioimmunoassay of plasma progesterone. J Clin Endocrinol Metab. 1971; 32, 619–624.CrossRefGoogle ScholarPubMed
Sengupta, P. The laboratory rat: relating its age with human’s. Int J Prev Med. 2013; 4, 624–630.Google Scholar
McCutcheon, JE, Marinelli, M. Age matters. Eur J Neurosci. 2009; 29, 997–1014.CrossRefGoogle ScholarPubMed
Spear, LP. The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev. 2000; 24, 417–463.CrossRefGoogle ScholarPubMed
Jahanfar, S, Eden, JA, Warren, P, Seppälä, M, Nguyen, TV. A twin study of polycystic ovary syndrome. Fertil Steril. 1995; 63, 478–486.CrossRefGoogle ScholarPubMed
Bateson, P, Gluckman, P, Hanson, M. The biology of developmental plasticity and the predictive adaptive response hypothesis. J Physiol. 2014; 592, 2357–2368.CrossRefGoogle ScholarPubMed
Zielinski, WJ, Vandenbergh, JG, Montano, MM. Effects of social stress and intrauterine position on sexual phenotype in wild-type house mice (Mus musculus). Physiol Behav. 1991; 49, 117–123.CrossRefGoogle Scholar
Maliqueo, M, Lara, HE, Sánchez, F, Echiburú, B, Crisosto, N, Sir-Petermann, T. Placental steroidogenesis in pregnant women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013; 166, 151–155.CrossRefGoogle ScholarPubMed
Sun, M, Maliqueo, M, Benrick, A, et al. Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring. Am J Physiol Endocrinol Metab. 2012; 303, E1373–E1385.CrossRefGoogle ScholarPubMed
Puttabyatappa, M, Cardoso, RC, Herkimer, C, Veiga-Lopez, A, Padmanabhan, V. Developmental programming: postnatal estradiol modulation of prenatally organized reproductive neuroendocrine function in sheep. Reproduction. 2016; 152, 139–150.CrossRefGoogle Scholar
Abbott, DH, Bruns, CR, Barnett, DK, et al. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring. Am J Physiol Endocrinol Metab. 2010; 299, E741–E751.CrossRefGoogle ScholarPubMed
Luense, LJ, Veiga-Lopez, A, Padmanabhan, V, Christenson, LK. Developmental programming: gestational testosterone treatment alters fetal ovarian gene expression. Endocrinology. 2011; 152, 4974–4983.CrossRefGoogle ScholarPubMed
Fujikura, T, Froehlich, LA. Organ-weight/brain-weight ratios as a parameter of prenatal growth: a balanced growth theory of visceras. Am J Obstet Gynecol. 1972; 112, 896–902.CrossRefGoogle ScholarPubMed
Mitropoulos, G., Scurry, J., Cussen, L. Organ weight/bodyweight ratios: growth rates of fetal organs in the latter half of pregnancy with a simple method for calculating mean organ weights. J Paediatr Child Health. 2008; 28, 236–239.CrossRefGoogle Scholar
Cabrero, A, Cubero, M, Llaverías, G, et al. Leptin down-regulates peroxisome proliferator-activated receptor gamma (PPAR-gamma) mRNA levels in primary human monocyte-derived macrophages. Mol Cell Biochem. 2005; 275, 173–179.CrossRefGoogle ScholarPubMed
Mirzaei, K, Hossein-Nezhad, A, Keshavarz, SA, et al. Crosstalk between circulating peroxisome proliferator-activated receptor gamma, adipokines and metabolic syndrome in obese subjects. Diabetol Metab Syndr. 2013; 5, 79.CrossRefGoogle ScholarPubMed
Keller, H, Givel, F, Perroud, M, Wahli, W. Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements. Mol Endocrinol. 1995; 9, 794–804.Google ScholarPubMed
Nuñez, SB, Medin, JA, Braissant, O, et al. Retinoid X receptor and peroxisome proliferator-activated receptor activate an estrogen responsive gene independent of the estrogen receptor. Mol Cell Endocrinol. 1997; 127, 27–40.CrossRefGoogle ScholarPubMed
Yanase, T, Mu, YM, Nishi, Y, et al. Regulation of aromatase by nuclear receptors. J Steroid Biochem Mol Biol. 2001; 79, 187–192.CrossRefGoogle ScholarPubMed
Lovekamp-Swan, T, Jetten, AM, Davis, BJ. Dual activation of PPARα and PPARγ by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells. Mol Cell Endocrinol. 2003; 201, 133–141.CrossRefGoogle ScholarPubMed
Barkan, D, Jia, H, Dantes, A, Vardimon, L, Amsterdam, A, Rubinstein, M. Leptin modulates the glucocorticoid-induced ovarian steroidogenesis. Endocrinology. 1999; 140, 1731–1738.CrossRefGoogle ScholarPubMed
Kendall, NR, Gutierrez, CG, Scaramuzzi, RJ, Baird, DT, Webb, R, Campbell, BK. Direct in vivo effects of leptin on ovarian steroidogenesis in sheep. Reproduction. 2004; 128, 757–765.CrossRefGoogle Scholar
Karamouti, M, Kollia, P, Kallitsaris, A, Vamvakopoulos, N, Kollios, G, Messinis, IE. Modulating effect of leptin on basal and follicle stimulating hormone-stimulated steroidogenesis in cultured human lutein granulosa cells. J Endocrinol Invest. 2009; 32, 415–419.CrossRefGoogle ScholarPubMed
Wang, Q, Kim, JY, Xue, K, Liu, J, Leader, A, Tsang, BK. Chemerin, a novel regulator of follicular steroidogenesis and its potential involvement in polycystic ovarian syndrome. Endocrinology. 2012; 153, 5600–5611.CrossRefGoogle ScholarPubMed
Wang, Q, Leader, A, Tsang, BK. Inhibitory roles of prohibitin and chemerin in FSH-induced rat granulosa cell steroidogenesis. Endocrinology. 2013; 154, 956–967.CrossRefGoogle ScholarPubMed
Cornejo, MP, Hentges, ST, Maliqueo, M, Coirini, H, Becu-Villalobos, D, Elias, CF. Neuroendocrine regulation of metabolism. J Neuroendocrinol. 2016; 28. doi: 10.1111/jne.12395.CrossRefGoogle ScholarPubMed
Wang, L, Shao, YY, Ballock, RT. Leptin antagonizes peroxisome proliferator-activated receptor-γ signaling in growth plate chondrocytes. PPAR Res. 2012; 2012, 9. doi: 10.1155/2012/756198.CrossRefGoogle ScholarPubMed
Abbasi, A, Moghadam, AA, Kahrarian, Z, Abbsavaran, R, Yari, K, Alizadeh, E. Molecular effects of leptin on peroxisome proliferator-activated receptor gamma (PPAR-γ) mRNA expression in rat’s adipose and liver tissue. Cell Mol Biol (Noisy-le-grand). 2017; 63, 89–93.CrossRefGoogle ScholarPubMed
Jenks, MZ, Fairfield, HE, Johnson, EC, Morrison, RF, Muday, GK. Sex steroid hormones regulate leptin transcript accumulation and protein secretion in 3T3-L1 cells. Sci Rep. 2017; 7, 8232.CrossRefGoogle ScholarPubMed
Dobrzyn, K, Smolinska, N, Kiezun, M, et al. Adiponectin: a new regulator of female reproductive system. Int J Endocrinol. 2018; 2018, 12. doi: 10.1155/2018/7965071.CrossRefGoogle ScholarPubMed
Ledoux, S, Campos, DB, Lopes, FL, Dobias-Goff, M, Palin, M-F, Murphy, BD. Adiponectin induces periovulatory changes in ovarian follicular cells. Endocrinology. 2006; 147, 5178–5186.CrossRefGoogle ScholarPubMed
Michalakis, KG, Segars, JH. The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction. Fertil Steril. 2010; 94, 1949–1957.CrossRefGoogle ScholarPubMed
Ishida, M, Shimabukuro, M, Yagi, S, et al. MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism. PLoS One. 2014; 9, e111537.CrossRefGoogle ScholarPubMed
Xu, S, Linher-Melville, K, Yang, BB, Wu, D, Li, J. Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting aromatase. Endocrinology. 2011; 152, 3941–3951.CrossRefGoogle ScholarPubMed
Foecking, EM, Szabo, M, Schwartz, NB, Levine, JE. Neuroendocrine consequences of prenatal androgen exposure in the female rat: absence of luteinizing hormone surges, suppression of progesterone receptor gene expression, and acceleration of the gonadotropin-releasing hormone pulse generator. Biol Reprod. 2005; 72, 1475–1483.CrossRefGoogle ScholarPubMed
Yan, X, Yuan, C, Zhao, N, Cui, Y, Liu, J. Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats. J Endocrinol. 2014; 222, 73–85.CrossRefGoogle ScholarPubMed
Hunzicker-Dunn, M, Maizels, ET. FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A. Cell Signal. 2006; 18, 1351–1359.CrossRefGoogle ScholarPubMed
Raju, GAR, Chavan, R, Deenadayal, M, et al. Luteinizing hormone and follicle stimulating hormone synergy: a review of role in controlled ovarian hyper-stimulation. J Hum Reprod Sci. 2013; 6, 227–234.CrossRefGoogle ScholarPubMed
Chang, RJ, Cook-Andersen, H. Disordered follicle development. Mol Cell Endocrinol. 2013; 373, 51–60.CrossRefGoogle ScholarPubMed
Noroozzadeh, M, Behboudi-Gandevani, S, Zadeh-Vakili, A, Ramezani Tehrani, F. Hormone-induced rat model of polycystic ovary syndrome: a systematic review. Life Sci. 2017; 191, 259–272.CrossRefGoogle ScholarPubMed
Wu, XY, Li, ZL, Wu, CY, et al. Endocrine traits of polycystic ovary syndrome in prenatally androgenized female Sprague–Dawley rats. Endocr J. 2010; 57, 201–209.CrossRefGoogle ScholarPubMed
Caligioni, CS. Assessing reproductive status/stages in mice. Curr Protoc Neurosci. 2009; 48: A.4I.1–A.4I.8. doi: 10.1002/0471142301.nsa04is48.CrossRefGoogle Scholar
Greenwald, GS, Rothchild, I. Formation and maintenance of corpora lutea in laboratory animals. J Anim Sci. 1968; 27 Suppl 1, 139–162.Google Scholar
Carmina, E, Oberfield, SE, Lobo, RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol. 2010; 203, 201.e1–201.e5.CrossRefGoogle Scholar
Lagaly, DV, Aad, PY, Grado-Ahuir, JA, Hulsey, LB, Spicer, LJ. Role of adiponectin in regulating ovarian theca and granulosa cell function. Mol Cell Endocrinol. 2008; 284, 38–45.CrossRefGoogle ScholarPubMed
Veldhuis, JD, Zhang, G, Garmey, JC. Troglitazone, an insulin-sensitizing thiazolidinedione, represses combined stimulation by LH and insulin of de Novo Androgen Biosynthesis by Thecal Cells in vitro. J Clin Endocrinol Metab. 2002; 87, 1129–1133.CrossRefGoogle ScholarPubMed
Reverchon, M, Cornuau, M, Ramé, C, Guerif, F, Royère, D, Dupont, J. Chemerin inhibits IGF-1-induced progesterone and estradiol secretion in human granulosa cells. Hum Reprod. 2012; 27, 1790–1800.CrossRefGoogle ScholarPubMed
Kitawaki, J, Kusuki, I, Koshiba, H, Tsukamoto, K, Honjo, H. Leptin directly stimulates aromatase activity in human luteinized granulosa cells. Mol Hum Reprod. 1999; 5, 708–713.CrossRefGoogle ScholarPubMed
Fan, W, Yanase, T, Morinaga, H, et al. Activation of peroxisome proliferator-activated receptor-γ and retinoid X receptor inhibits aromatase transcription via nuclear factor-κB. Endocrinology. 2005; 146, 85–92.CrossRefGoogle ScholarPubMed