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Prenatal testosterone exposure decreases colocalization of insulin receptors in kisspeptin/neurokinin B/dynorphin and agouti‐related peptide neurons of the adult ewe

dc.contributor.authorCernea, Maria
dc.contributor.authorPhillips, Rebecca
dc.contributor.authorPadmanabhan, Vasantha
dc.contributor.authorCoolen, Lique M.
dc.contributor.authorLehman, Michael N.
dc.date.accessioned2016-11-18T21:24:05Z
dc.date.available2017-12-01T21:54:12Zen
dc.date.issued2016-10
dc.identifier.citationCernea, Maria; Phillips, Rebecca; Padmanabhan, Vasantha; Coolen, Lique M.; Lehman, Michael N. (2016). "Prenatal testosterone exposure decreases colocalization of insulin receptors in kisspeptin/neurokinin B/dynorphin and agouti‐related peptide neurons of the adult ewe." European Journal of Neuroscience 44(8): 2557-2568.
dc.identifier.issn0953-816X
dc.identifier.issn1460-9568
dc.identifier.urihttps://hdl.handle.net/2027.42/134470
dc.description.abstractInsulin serves as a link between the metabolic and reproductive systems, communicating energy availability to the hypothalamus and enabling reproductive mechanisms. Adult Suffolk ewes prenatally exposed to testosterone (T) display an array of reproductive and metabolic dysfunctions similar to those seen in women with polycystic ovarian syndrome (PCOS), including insulin resistance. Moreover, prenatal T treatment alters neuropeptide expression in KNDy (co‐expressing kisspeptin, neurokinin B/dynorphin) and agouti‐related peptide (AgRP) neurons in the arcuate nucleus, two populations that play key roles in the control of reproduction and metabolism, respectively. In this study, we determined whether prenatal T treatment also altered insulin receptors in KNDy and AgRP neurons, as well as in preoptic area (POA) kisspeptin, pro‐opiomelanocortin (POMC), and gonadotropin‐releasing hormone (GnRH) neurons of the adult sheep brain. Immunofluorescent detection of the beta subunit of insulin receptor (IRβ) revealed that KNDy, AgRP and POMC neurons, but not GnRH or POA kisspeptin neurons, colocalize IRβ in control females. Moreover, prenatal T treatment decreased the percentage of KNDy and AgRP neurons that colocalized IRβ, consistent with reduced insulin sensitivity. Administration of the anti‐androgen drug, Flutamide, during prenatal T treatment, prevented the reduction in IRβ colocalization in AgRP, but not in KNDy neurons, suggesting that these effects are programmed by androgenic and oestrogenic actions, respectively. These findings provide novel insight into the effects of prenatal T treatment on hypothalamic insulin sensitivity and raise the possibility that decreased insulin receptors, specifically within KNDy and AgRP neurons, may contribute to the PCOS‐like phenotype of this animal model.Long‐term consequences of prenatal T treatment on insulin receptor beta (IRβ) colocalization within AgRP, POMC and KNDy neurons of the female sheep hypothalamus. Decreased IRβ colocalization within AgRP and KNDy neurons may result in decreased insulin sensitivity in these neurons and altered steroid feedback control of GnRH secretion, thereby contributing to the metabolic and reproductive disruptions seen in the PCOS‐like phenotype of this animal model.
dc.publisherHumana Press
dc.publisherWiley Periodicals, Inc.
dc.subject.otherpolycystic ovarian syndrome
dc.subject.otherkisspeptin
dc.subject.othersheep
dc.subject.otherinsulin receptor
dc.subject.otheragouti‐related peptide
dc.titlePrenatal testosterone exposure decreases colocalization of insulin receptors in kisspeptin/neurokinin B/dynorphin and agouti‐related peptide neurons of the adult ewe
dc.typeArticleen_US
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelNeurosciences
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/134470/1/ejn13373_am.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/134470/2/ejn13373-sup-0001-SupInfo.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/134470/3/ejn13373.pdf
dc.identifier.doi10.1111/ejn.13373
dc.identifier.sourceEuropean Journal of Neuroscience
dc.identifier.citedreferencePoretsky, L. & Kalin, M.F. ( 1987 ) The gonadotropic function of insulin. Endocr. Rev., 8, 132 – 141.
dc.identifier.citedreferenceQiu, X., Dowling, A.R., Marino, J.S., Faulkner, L.D., Bryant, B., Brüning, J.C., Elias, C.F. & Hill, J.W. ( 2013 ) Delayed puberty but normal fertility in mice with selective deletion of insulin receptors from Kiss1 cells. Endocrinology, 154, 1337 – 1348.
dc.identifier.citedreferenceQu, S.Y., Yang, Y.K., Li, J.Y., Zeng, Q. & Gantz, I. ( 2001 ) Agouti‐related protein is a mediator of diabetic hyperphagia. Regul. Peptides, 98, 69 – 75.
dc.identifier.citedreferenceRecabarren, S.E., Padmanabhan, V., Codner, E., Lobos, A., Durán, C., Vidal, M., Foster, D.L. & Sir‐Petermann, T. ( 2005 ) Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone. Am. J. Physiol‐Endoc. M., 289, E801 – E806.
dc.identifier.citedreferenceRoa, J. & Herbison, A.E. ( 2012 ) Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice. Endocrinology, 153, 5587 – 5599.
dc.identifier.citedreferenceRobinson, J.E., Forsdike, R.A. & Taylor, J.A. ( 1999 ) In utero exposure of female lambs to testosterone reduces the sensitivity of the gonadotropin‐releasing hormone neuronal network to inhibition by progesterone. Endocrinology, 140, 5797 – 5805.
dc.identifier.citedreferenceRondini, T.A., Baddini, S.P., Sousa, L.F., Bittencourt, J.C. & Elias, C.F. ( 2004 ) Hypothalamic cocaine‐ and amphetamine‐regulated transcript neurons project to areas expressing gonadotropin releasing hormone immunoreactivity and to the anteroventral periventricular nucleus in male and female rats. Neuroscience, 125, 735 – 748.
dc.identifier.citedreferencede Roux, N., Genin, E., Carel, J.C., Matsuda, F., Chaussain, J.L. & Milgrom, E. ( 2003 ) Hypogonadotropic hypogonadism due to loss of function of the KiSS1‐derived peptide receptor GPR54. Proc. Natl. Acad. Sci. USA, 100, 10972 – 10976.
dc.identifier.citedreferenceSarma, H.N., Manikkam, M., Herkimer, C., Dell’Orco, J., Welch, K.B., Foster, D.L. & Padmanabhan, V. ( 2005 ) Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle‐stimulating hormone responsiveness, to estradiol negative feedback in the female. Endocrinology, 146, 4281 – 4291.
dc.identifier.citedreferenceSeminara, S.B., Messager, S., Chatzidaki, E.E., Thresher, R.R., Acierno, J.S. Jr, Shagoury, J.K., Bo‐Abbas, Y., Kuohung, W. et al. ( 2003 ) The GPR54 gene as a regulator of puberty. New Engl. J. Med., 349, 1614 – 1627.
dc.identifier.citedreferenceSharma, T.P., Herkimer, C., West, C., Ye, W., Birch, R., Robinson, J.E., Foster, D.L. & Padmanabhan, V. ( 2002 ) Fetal programming: prenatal androgen disrupts positive feedback actions of estradiol but does not affect timing of puberty in female sheep. Biol. Reprod., 66, 924 – 933.
dc.identifier.citedreferenceSheppard, K.M., Padmanabhan, V., Coolen, L.M. & Lehman, M.N. ( 2011 ) Prenatal programming by testosterone of hypothalamic metabolic control neurones in the ewe. J. Neuroendocrinol., 23, 401 – 411.
dc.identifier.citedreferenceSirmans, S.M. & Pate, K.A. ( 2014 ) Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin. Epidemiol., 6, 1 – 13.
dc.identifier.citedreferenceSmith, J.T., Li, Q., Yap, K.S., Shahab, M., Roseweir, A.K., Millar, R.P. & Clarke, I.J. ( 2011 ) Kisspeptin is essential for the full preovulatory LH surge and stimulates GnRH release from the isolated ovine median eminence. Endocrinology, 152, 1001 – 1012.
dc.identifier.citedreferenceSteckler, T., Manikkam, M., Inskeep, E.K. & Padmanabhan, V. ( 2007 ) Developmental programming: follicular persistence in prenatal testosterone‐treated sheep is not programmed by androgenic actions of testosterone. Endocrinology, 148, 3532 – 3540.
dc.identifier.citedreferenceSteckler, T.L., Herkimer, C., Dumesic, D.A. & Padmanabhan, V. ( 2009 ) Developmental programming: excess weight gain amplifies the effects of prenatal testosterone excess on reproductive cyclicity – implication to PCOS. Endocrinology, 150, 1456 – 1465.
dc.identifier.citedreferenceSullivan, S.D. & Moenter, S.M. ( 2004 ) y‐Aminobutyric acid neurons integrate and rapidly transmit permissive and inhibitory metabolic cues to gonadotropin‐releasing hormone neurons. Endocrinology, 145, 1194 – 1202.
dc.identifier.citedreferenceUnsworth, W.P., Taylor, J.A. & Robinson, J.E. ( 2005 ) Prenatal programming of reproductive neuroendocrine function: the effect of prenatal androgens on the development of estrogen positive feedback and ovarian cycles in the ewe. Biol. Reprod., 72, 619 – 627.
dc.identifier.citedreferenceVeiga‐Lopez, A., Ye, W., Phillips, D.J., Herkimer, C., Knight, P.G. & Padmanabhan, V. ( 2008 ) Developmental programming: deficits in reproductive hormone dynamics and ovulatory outcomes in prenatal, testosterone‐treated sheep. Biol. Reprod., 78, 636 – 647.
dc.identifier.citedreferenceVeiga‐Lopez, A., Astapova, O.I., Aizenberg, E.F., Lee, J.S. & Padmanabhan, V. ( 2009 ) Developmental programming: contribution of prenatal androgen and estrogen to estradiol feedback systems and periovulatory hormonal dynamics in sheep. Biol. Reprod., 80, 718 – 725.
dc.identifier.citedreferenceVeiga‐Lopez, A., Lee, J.S. & Padmanabhan, V. ( 2010 ) Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone‐treated female sheep. Endocrinology, 151, 4007 – 4017.
dc.identifier.citedreferenceVeiga‐Lopez, A., Steckler, T.L., Abbott, D.H., Welch, K.B., MohanKumar, P.S., Phillips, D.J., Refsal, K. & Padmanabhan, V. ( 2011 ) Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep. Biol. Reprod., 84, 87 – 96.
dc.identifier.citedreferenceVulliémoz, N.R., Xiao, E., Xia‐Zhang, L., Wardlaw, S.L. & Ferin, M. ( 2005 ) Central infusion of agouti‐related peptide suppresses pulsatile luteinizing hormone release in the ovariectomized rhesus monkey. Endocrinology, 146, 784 – 789.
dc.identifier.citedreferenceWakabayashi, Y., Nakada, T., Murata, K., Ohkura, S., Mogi, K., Navarro, V.M., Clifton, D.K., Mori, Y. et al. ( 2010 ) Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin‐releasing hormone secretion in the goat. J. Neurosci., 30, 3124 – 3132.
dc.identifier.citedreferenceWood, R.I. & Foster, D.L. ( 1998 ) Sexual differentiation of reproductive neuroendocrine function in sheep. Rev. Reprod., 3, 130 – 140.
dc.identifier.citedreferenceAbbott, D.H., Bruns, C.M., Barnett, D.K., Tarantal, A.F., Hoffmann, S.M., Zhou, R., Levine, J.E. & Dumesic, D.A. ( 2008 ) Fetal origins of the polycystic ovarian syndrome. In Dunaif, A., Chang, R.J., Franks, S. & Legro, R.S. (Eds), Polycystic Ovarian Syndrome, 1st Edn. Humana Press, Totowa, NJ, pp. 87 – 106.
dc.identifier.citedreferenceAbbott, M.A., Wells, D.G. & Fallon, J.R. ( 1999 ) The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J. Neurosci., 19, 7300 – 7308.
dc.identifier.citedreferenceAbi‐Salloum, B., Herkimer, C., Lee, J.S., Veiga‐Lopez, A. & Padmanabhan, V. ( 2012 ) Developmental programming: prenatal and postnatal contribution of androgens and insulin in the reprogramming of estradiol positive feedback disruptions in prenatal testosterone‐treated sheep. Endocrinology, 153, 2813 – 2822.
dc.identifier.citedreferenceAdam, C.L., Findlay, P.A., Kyle, C.E., Young, P. & Mercer, J.G. ( 1997 ) Effect of chronic food restriction on pulsatile luteinizing hormone secretion and hypothalamic neuropeptide Y gene expression in castrate male sheep. J. Endocrinol., 152, 329 – 337.
dc.identifier.citedreferenceAdashi, E.Y., Hsueh, A.J. & Yen, S.S. ( 1981 ) Insulin enhancement of luteinizing hormone and follicle‐stimulating hormone release by cultured pituitary cells. Endocrinology, 108, 1441 – 1449.
dc.identifier.citedreferenceBackholer, K., Smith, J.T., Rao, A., Pereira, A., Iqbal, J., Ogawa, S., Li, Q. & Clarke, I.J. ( 2010 ) Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells. Endocrinology, 151, 2233 – 2243.
dc.identifier.citedreferenceBaillargeon, J.P., Jakubowicz, D.J., Iuorno, M.J., Jakubowicz, S. & Nestler, J.E. ( 2004 ) Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil. Steril., 82, 893 – 902.
dc.identifier.citedreferenceBenoit, S.C., Air, E.L., Coolen, L.M., Strauss, R., Jackman, A., Clegg, D.J., Seeley, R.J. & Woods, S.C. ( 2002 ) The catabolic action of insulin in the brain is mediated by melanocortins. J. Neurosci., 22, 9048 – 9052.
dc.identifier.citedreferenceBeymer, M., Aziz, R., Mayer, C., Fukuda, M., Lin, R.Z., Boehm, U. & Acosta‐Martinez, M. ( 2012 ) The effects of a Kisspeptin‐cell specific deletion of PI3K catalytic subunits p110α and p110β on the hypothalamic‐pituitary‐gonadal axis. Endocr. Rev., 33, SUN‐701.
dc.identifier.citedreferenceBirch, R.A., Padmanabhan, V., Foster, D.L., Unsworth, W.P. & Robinson, J.E. ( 2003 ) Prenatal programming of reproductive neuroendocrine function: fetal androgen exposure produces progressive disruption of reproductive cycles in sheep. Endocrinology, 144, 1426 – 1434.
dc.identifier.citedreferenceBreen, T.L., Conwell, I.M. & Wardlaw, S.L. ( 2005 ) Effects of fasting, leptin, and insulin on AGRP and POMC peptide release in the hypothalamus. Brain Res., 1032, 141 – 148.
dc.identifier.citedreferenceBruning, J.C., Gautam, D., Burks, D.J., Gillette, J., Schubert, M., Orban, P.C., Klein, R., Krone, W. et al. ( 2000 ) Role of brain insulin receptor in control of body weight and reproduction. Science, 289, 2122 – 2125.
dc.identifier.citedreferenceBurcelin, R., Thorens, B., Glauser, M., Gaillard, R.C. & Pralong, F.P. ( 2003 ) Gonadotropin‐releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin. Endocrinology, 144, 4484 – 4491.
dc.identifier.citedreferenceBurks, D.J., de Mora, J.F., Schubert, M., Withers, D.J., Myers, M.G., Towery, H.H., Altamuro, S.L., Flint, C.L. et al. ( 2000 ) IRS‐2 pathways integrate female reproduction and energy homeostasis. Nature, 407, 377 – 382.
dc.identifier.citedreferenceCaraty, A., Smith, J.T., Lomet, D., Ben Said, S., Morrissey, A., Cognie, J., Doughton, B., Baril, G. et al. ( 2007 ) Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes. Endocrinology, 148, 5258 – 5267.
dc.identifier.citedreferenceCardoso, R.C., Veiga‐Lopez, A., Moeller, J., Beckett, E., Pease, A., Keller, E., Madrigal, V., Chazenbalk, G. et al. ( 2016 ) Developmental programming: impact of gestational steroid and metabolic milieus on adiposity and insulin sensitivity in prenatal testosterone‐treated female sheep. Endocrinology, 157, 522 – 535.
dc.identifier.citedreferenceCastellano, J.M., Navarro, V.M., Fernandez‐Fernandez, R., Nogueiras, R., Tovar, S., Roa, J., Vazquez, M.J., Vigo, E. et al. ( 2005 ) Changes in hypothalamic KiSS‐1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition. Endocrinology, 146, 3917 – 3925.
dc.identifier.citedreferenceCastellano, J.M., Navarro, V.M., Fernández‐Fernández, R., Roa, J., Vigo, E., Pineda, R., Dieguez, C., Aguilar, E. et al. ( 2006 ) Expression of hypothalamic KiSS‐1 system and rescue of defective gonadotropic responses by kisspeptin in streptozotocin‐induced diabetic male rats. Diabetes, 55, 2602 – 2610.
dc.identifier.citedreferenceCastellano, J.M., Navarro, V.M., Roa, J., Pineda, R., Sanchez‐Garrido, M.A., Garcia‐Galiano, D., Vigo, E., Dieguez, C. et al. ( 2009 ) Alterations in hypothalamic KiSS‐1 system in experimental diabetes: early changes and functional consequences. Endocrinology, 150, 784 – 794.
dc.identifier.citedreferenceCastellano, J.M., Bentsen, A.H., Mikkelsen, J.D. & Tena‐Sempere, M. ( 2010 ) Kisspeptins: Bridging energy homeostasis and reproduction. Brain Res., 1364, 129 – 138.
dc.identifier.citedreferenceCernea, M., Padmanabhan, V., Goodman, R.L., Coolen, L.M. & Lehman, M.N. ( 2015 ) Prenatal testosterone treatment leads to changes in the morphology of KNDy neurons, their inputs, and projections to GnRH cells in female sheep. Endocrinology, 156, 3277 – 3291.
dc.identifier.citedreferenceCheng, G., Coolen, L.M., Padmanabhan, V., Goodman, R.L. & Lehman, M.N. ( 2010 ) The kisspeptin/neurokinin B/dynorphin (KNDy) cell population of the arcuate nucleus: sex differences and effects of prenatal testosterone in sheep. Endocrinology, 151, 301 – 311.
dc.identifier.citedreferenceClarke, I.J., Scaramuzzi, R.J. & Short, R.V. ( 1977 ) Ovulation in prenatally androgenized ewes. J. Endocrinol., 73, 385 – 389.
dc.identifier.citedreferenceCohen, J. ( 1992 ) A power primer. Psychol. Bull., 112, 155 – 159.
dc.identifier.citedreferenceDiVall, S.A., Williams, T.R., Carver, S.E., Koch, L., Bruning, J.C., Kahn, C.R., Wondisford, F., Radovick, S. et al. ( 2010 ) Divergent roles of growth factors in the GnRH regulation of puberty in mice. J. Clin. Invest., 120, 2900 – 2909.
dc.identifier.citedreferenceDumesic, D.A., Abbott, D.H. & Padmanabhan, V. ( 2007 ) Polycystic ovary syndrome and its developmental origins. Rev. Endocr. Metab. Dis., 8, 127 – 141.
dc.identifier.citedreferenceDunaif, A. ( 1997 ) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr. Rev., 18, 774 – 800.
dc.identifier.citedreferenceDungan, H.M., Gottsch, M.L., Zeng, H., Gragerov, A., Bergmann, J.E., Vassilatis, D.K., Clifton, D.K. & Steiner, R.A. ( 2007 ) The role of kisspeptin‐GPR54 signaling in the tonic regulation and surge release of gonadotropin‐releasing hormone/luteinizing hormone. J. Neurosci., 27, 12088 – 12095.
dc.identifier.citedreferenceEvans, M.C., Rizwan, M., Mayer, C., Boehm, U. & Anderson, G.M. ( 2014a ) Evidence that insulin signalling in gonadotrophin‐releasing hormone and kisspeptin neurones does not play an essential role in metabolic regulation of fertility in mice. J. Neuroendocrinol., 26, 468 – 479.
dc.identifier.citedreferenceEvans, M.C., Rizwan, M.Z. & Anderson, G.M. ( 2014b ) Insulin action on GABA neurons is a critical regulator of energy balance but not fertility in mice. Endocrinology, 155, 4368 – 4379.
dc.identifier.citedreferenceFranks, S. ( 1995 ) Polycystic ovary syndrome. New Engl. J. Med., 333, 853 – 861.
dc.identifier.citedreferenceFu, L.Y. & van den Pol, A.N. ( 2010 ) Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism. J. Neurosci., 30, 10205 – 10219.
dc.identifier.citedreferenceHahn, T.M., Breininger, J.F., Baskin, D.G. & Schwartz, M.W. ( 1998 ) Coexpression of Agrp and NPY in fasting‐activated hypothalamic neurons. Nat. Neurosci., 1, 271 – 272.
dc.identifier.citedreferenceHeras‐Sandoval, D., Ferrera, P. & Arias, C. ( 2012 ) Amyloid‐β protein modulates insulin signaling in presynaptic terminals. Neurochem. Res., 37, 1879 – 1885.
dc.identifier.citedreferenceHolte, J. ( 1996 ) Disturbances in insulin secretion and sensitivity in women with the polycystic ovary syndrome. Bailliere. Clin. Endoc., 10, 221 – 247.
dc.identifier.citedreferenceHouten, M., Posner, B.I., Kopriwa, B.M. & Brawer, J.R. ( 1980 ) Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus. Science, 207, 1081.
dc.identifier.citedreferenceIremonger, K.J. & Herbison, A.E. ( 2015 ) Multitasking in gonadotropin‐releasing hormone neuron dendrites. Neuroendocrinology, 102, 1 – 7.
dc.identifier.citedreferenceJackson, L.M., Timmer, K.M. & Foster, D.L. ( 2008 ) Sexual differentiation of the external genitalia and the timing of puberty in the presence of an antiandrogen in sheep. Endocrinology, 149, 4200 – 4208.
dc.identifier.citedreferenceJansen, H.T., Cutter, C., Hardy, S., Lehman, M.N. & Goodman, R.L. ( 2003 ) Seasonal plasticity within the GnRH system of the ewe: changes in identified GnRH inputs and in glial association. Endocrinology, 144, 3663 – 3676.
dc.identifier.citedreferenceKim, H.H., DiVall, S.A., Deneau, R.M. & Wolfe, A. ( 2005 ) Insulin regulation of GnRH gene expression through MAP kinase signaling pathways. Mol. Cell. Endocrinol., 242, 42 – 49.
dc.identifier.citedreferenceKlenke, U., Constantin, S. & Wray, S. ( 2010 ) Neuropeptide Y directly inhibits neuronal activity in a subpopulation of gonadotropin‐releasing hormone‐1 neurons viaY1receptors. Endocrinology, 151, 2736 – 2746.
dc.identifier.citedreferenceKönner, A.C., Janoschek, R., Plum, L., Jordan, S.D., Rother, E., Ma, X., Xu, C., Enriori, P. et al. ( 2007 ) Insulin action in AgRP‐expressing neurons is required for suppression of hepatic glucose production. Cell Metab., 5, 438 – 449.
dc.identifier.citedreferenceLegro, R.S., Zaino, R.J., Demers, L.M., Kunselman, A.R., Gnatuk, C.L., Williams, N.I. & Dodson, W.C. ( 2007 ) The effects of metformin and rosiglitazone, alone and in combination, on the ovary and endometrium in polycystic ovary syndrome. Am. J. Obstet. Gynecol., 196, 402.
dc.identifier.citedreferenceLehman, M.N., Coolen, L.M. & Goodman, R.L. ( 2010 ) Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin‐releasing hormone secretion. Endocrinology, 151, 3479 – 3489.
dc.identifier.citedreferenceLehman, M.N., Hileman, S.M. & Goodman, R.L. ( 2013 ) Neuroanatomy of the kisspeptin signaling system in mammals: comparative and developmental aspects. In Kauffman, A. & Smith, J. (Eds), Chapter 3 in Kisspeptin Signaling in Reproductive Biology. Advances in Experimental Medicine and Biology, vol 784. Springer‐Verlag, New York, pp. 27 – 62.
dc.identifier.citedreferenceLennette, D.A. ( 1978 ) An improved mounting medium for immunofluorescence microscopy. Am. J. Clin. Pathol., 69, 647 – 648.
dc.identifier.citedreferenceLeranth, C., MacLusky, N.J., Shanabrough, M. & Naftolin, F. ( 1988 ) Immunohistochemical evidence for synaptic connections between pro‐opiomelanocortinimmunoreactive axons and LH‐RH neurons in the preoptic area of the rat. Brain Res., 449, 167 – 176.
dc.identifier.citedreferenceLi, C., Chen, P. & Smith, M.S. ( 1999 ) Morphological evidence for direct interaction between arcuate nucleus neuropeptide Y (NPY) neurons and gonadotropin‐releasing hormone neurons and the possible involvement of NPY Y1 receptors. Endocrinology, 140, 5382 – 5390.
dc.identifier.citedreferenceLouis, G.W., Greenwald‐Yarnell, M., Phillips, R., Coolen, L.M., Lehman, M.N. & Myers, M.G. ( 2011 ) Molecular mapping of the neural pathways linking leptin to the neuroendocrine reproductive axis. Endocrinology, 152, 2302 – 2310.
dc.identifier.citedreferenceManikkam, M., Crespi, E.J., Doop, D.D., Herkimer, C., Lee, J.S., Yu, S., Brown, M.B., Foster, D.L. et al. ( 2004 ) Fetal programming: prenatal testosterone excess leads to fetal growth retardation and postnatal catch‐up growth in sheep. Endocrinology, 145, 790 – 798.
dc.identifier.citedreferenceManikkam, M., Steckler, T.L., Welch, K.B., Inskeep, E.K. & Padmanabhan, V. ( 2006 ) Fetal programming: prenatal testosterone treatment leads to follicular persistence/luteal defects; partial restoration of ovarian function by cyclic progesterone treatment. Endocrinology, 147, 1997 – 2007.
dc.identifier.citedreferenceMcShane, T.M., Petersen, S.L., McCrone, S. & Keisler, D.H. ( 1993 ) Influence of food restriction on neuropeptide‐Y, proopiomelanocortin, and luteinizing hormone‐releasing hormone gene expression in sheep hypothalami. Biol. Reprod., 49, 831 – 839.
dc.identifier.citedreferenceMerkley, C.M., Porter, K.L., Coolen, L.M., Hileman, S.M., Billings, H.J., Drews, S., Goodman, R.L. & Lehman, M.N. ( 2012 ) KNDy (Kisspeptin/Neurokinin B/Dynorphin) neurons are activated during both pulsatile and surge secretion of LH in the ewe. Endocrinology, 153, 5406 – 5414.
dc.identifier.citedreferenceMoret, M., Stettler, R., Rodieux, F., Gaillard, R.C., Waeber, G., Wirthner, D., Giusti, V., Tappy, L. et al. ( 2009 ) Insulin modulation of luteinizing hormone secretion in normal female volunteers and lean polycystic ovary syndrome patients. Neuroendocrinology, 89, 131 – 139.
dc.identifier.citedreferenceMorton, G.J. & Schwartz, M.W. ( 2001 ) The NPY/AgRP neuron and energy homeostasis. Int. J. Obes. Relat. Metab. Disord., 25, S56 – S62.
dc.identifier.citedreferenceNakagawa, S. & Cuthill, I.C. ( 2007 ) Effect size, confidence interval and statistical significance: a practical guide for biologists. Biol. Rev. Camb. Philos., 82, 591 – 605.
dc.identifier.citedreferenceNorgren, R.B. Jr & Lehman, M.N. ( 1989 ) A double label pre‐embedding immunoperoxidase technique for electron microscopy using diaminobenzidine and tetramethylbenzidine as markers. J. Histochem. and Cytochem., 37, 1283 – 1289.
dc.identifier.citedreferenceOkamoto, H., Nakae, J., Kitamura, T., Park, B.‐C., Dragatsis, I. & Accili, D. ( 2004 ) Transgenic rescue of insulin receptor–deficient mice. J. Clin. Invest., 114, 214 – 223.
dc.identifier.citedreferenceOkamura, H., Tsukamura, H., Ohkura, S., Uenoyama, Y., Wakabayashi, Y. & Maeda, K. ( 2013 ) Kisspeptin and GnRH pulse generation. Adv. Exp. Med. Biol., 784, 297 – 323.
dc.identifier.citedreferencePadmanabhan, V. & Veiga‐Lopez, A. ( 2011 ) Developmental origin of reproductive and metabolic dysfunctions: androgenic versus estrogenic reprogramming. Semin. Reprod. Med., 29, 173 – 186.
dc.identifier.citedreferencePadmanabhan, V. & Veiga‐Lopez, A. ( 2013 ) Sheep models of polycystic ovary syndrome phenotype. Mol. Cell. Endocrinol., 373, 8 – 20.
dc.identifier.citedreferencePadmanabhan, V., Manikkam, M., Recabarren, S. & Foster, D. ( 2006 ) Prenatal testosterone excess programs reproductive and metabolic dysfunction in the female. Mol. Cell. Endocrinol., 246, 165 – 174.
dc.identifier.citedreferencePadmanabhan, V., Sarma, H.N., Savabieasfahani, M., Steckler, T.L. & Veiga‐Lopez, A. ( 2010a ) Developmental reprogramming of reproductive and metabolic dysfunction in sheep: native steroids vs. environmental steroid receptor modulators. Int. J. Androl., 33, 394 – 404.
dc.identifier.citedreferencePadmanabhan, V., Veiga‐Lopez, A., Abbott, D.H., Recabarren, S.E. & Herkimer, C. ( 2010b ) Developmental programming: impact of prenatal testosterone excess and postnatal weight gain on insulin sensitivity index and transfer of traits to offspring of overweight females. Endocrinology, 151, 595 – 605.
dc.identifier.citedreferencePadmanabhan, V., Veiga‐Lopez, A., Herkimer, C., Salloum, B.A., Moeller, J., Beckett, E. & Sreedharan, R. ( 2015 ) Developmental programming: prenatal and postnatal androgen antagonist and insulin sensitizer interventions prevent advancement of puberty and improve LH surge dynamics in prenatal testosterone‐treated sheep. Endocrinology, 156, 2678 – 2692.
dc.identifier.citedreferencePark, C.W., Yoo, K.‐Y., Hwang, I.K., Choi, J.H., Lee, C.H., Park, O.K., Cho, J.H., Lee, Y.L. et al. ( 2009 ) Age‐related changes in the insulin receptor β in the gerbil hippocampus. Neurochem. Res., 34, 2154 – 2162.
dc.identifier.citedreferencePinilla, L., Aguilar, E., Dieguez, C., Millar, R.P. & Tena‐Sempere, M. ( 2012 ) Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol. Rev., 92, 1235 – 1316.
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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