TGFβ1 regulates prolactin secretion during postnatal development: gender differences

in Journal of Endocrinology
View More View Less
  • 1 Instituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina
  • 2 Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

Correspondence should be addressed to G Díaz-Torga: gdiaz@ibyme.conicet.gov.ar
Restricted access

Serum prolactin levels gradually increase from birth to puberty in both male and female rats, with higher levels observed in female since the first days of life. The increase in lactotroph secretion was attributed to the maturation of prolactin-inhibiting and prolactin-releasing factors; however, those mechanisms could not fully explain the gender differences observed. Prolactin secretion from isolated lactotrophs, in the absence of hypothalamic control, also increases during the first weeks of life, suggesting the involvement of intra-pituitary factors. We postulate that pituitary transforming growth factor beta 1 (TGFβ1) is involved in the regulation of prolactin secretion as well as in the gender differences observed at early postnatal age. Several components of the local TGFβ1 system were evaluated during postnatal development (11, 23, and 45 days) in female and male Sprague–Dawley rats. In vivo assays were performed to study local TGFβ1 activation and its impact on prolactin secretion. At day 11, female pituitaries present high levels of active TGFβ1, concomitant with the highest expression of TGFβ1 target genes and the phospho-Smad3 immunostaining in lactotrophs. The steady increase in prolactin secretion inversely correlates with active TGFβ1 levels only in females. Dopamine and estradiol induce TGFβ1 activation at day 11, in both genders, but its activation induces the inhibition of prolactin secretion only in females. Our findings demonstrate that: (1) TGFβ1 activation is regulated by dopamine and estradiol; (2) the inhibitory regulation of local TGFβ1 on prolactin secretion is gender specific; and (3) this mechanism is responsible, at least partially, for the gender differences observed being relevant during postnatal development.

 

      Society for Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 693 693 39
Full Text Views 66 66 2
PDF Downloads 25 25 1
  • Annes JP, Munger JS & Rifkin DB 2003 Making sense of latent TGFbeta activation. Journal of Cell Science 116 217224. (https://doi.org/10.1242/jcs.00229)

    • Search Google Scholar
    • Export Citation
  • Becú-Villalobos D, Lacau-Mengido IM, Díaz-Torga GS & Libertun C 1992 Ontogenic studies of the neural control of adenohypophyseal hormones in the rat. II. prolactin. Cellular and Molecular Neurobiology 12 119. (https://doi.org/10.1007/BF00711635)

    • Search Google Scholar
    • Export Citation
  • Ben-Jonathan N & Hnasko R 2001 Dopamine as a prolactin (PRL) inhibitor. Endocrine Reviews 22 724763. (https://doi.org/10.1210/edrv.22.6.0451)

    • Search Google Scholar
    • Export Citation
  • Brunschwig EB, Wilson K, Mack D, Dawson D, Lawrence E, Willson JKV, Lu SL, Nosrati A, Rerko RM, Swinler S, et al. 2003 PMEPA1, a transforming growth factor-β-induced marker of terminal colonocyte differentiation whose expression is maintained in primary and metastatic colon cancer. Cancer Research 63 15681575.

    • Search Google Scholar
    • Export Citation
  • Chen HT 1987 Postnatal development of pituitary lactotropes in the rat measured by reverse hemolytic plaque assay. Endocrinology 120 247253. (https://doi.org/10.1210/endo-120-1-247)

    • Search Google Scholar
    • Export Citation
  • Díaz-Torga GS, Becú-Villalobos D & Libertun C 1994 Ontogeny of angiotensin-II-induced prolactin release in vivo and in vitro in female and male rats. Neuroendocrinology 59 5762. (https://doi.org/10.1159/000126638)

    • Search Google Scholar
    • Export Citation
  • Faraoni EY, Camilletti MA, Abeledo-Machado A, Ratner LD, de Fino F, Ipo Huhtaniemi I, Rulli SB & Díaz-Torga G 2017 Sex differences in the development of prolactinoma in mice overexpressing hCGB: role of TGFB1. Journal of Endocrinology 232 535546. (https://doi.org/10.1530/JOE-16-0371)

    • Search Google Scholar
    • Export Citation
  • Fujiwara K, Ikeda H & Yoshimoto T 1995 Immunohistochemical demonstration of TGF-beta-receptor type II in human pituitary adenomas. Acta Histochemica 97 445454. (https://doi.org/10.1016/S0065-1281(11)80071-1)

    • Search Google Scholar
    • Export Citation
  • Grattan DR 2015 60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-prolactin axis. Journal of Endocrinology 226 T101T122. (https://doi.org/10.1530/JOE-15-0213)

    • Search Google Scholar
    • Export Citation
  • Jin L, Qian X, Kulig E, Sanno N, Scheithauer BW, Kovacs K, Young WF & Lloyd RV 1997 Transforming growth factor-β, transforming growth factor-β receptor II, and p27(Kip1) expression in nontumorous and neoplastic human pituitaries. American Journal of Pathology 151 509519.

    • Search Google Scholar
    • Export Citation
  • Kansra S, Yamagata S, Sneade L, Foster L & Ben-Jonathan N 2005 Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release. Molecular and Cellular Endocrinology 239 2736. (https://doi.org/10.1016/j.mce.2005.04.008)

    • Search Google Scholar
    • Export Citation
  • Karanth S, Dutt A & Juneja HS 1987 Age-related release of prolactin by the pituitary and the pituitary-hypothalamic complex in vitro: an attempt to describe the development of the hypothalamic prolactin-inhibiting and -releasing activities in male rats. Journal of Endocrinology 115 405409. (https://doi.org/10.1677/joe.0.1150405)

    • Search Google Scholar
    • Export Citation
  • Leong DA, Frawley LS & Neill JD 1983 Neuroendocrine control of prolactin secretion. Annual Review of Physiology 45 109127. (https://doi.org/10.1146/annurev.ph.45.030183.000545)

    • Search Google Scholar
    • Export Citation
  • Levy L & Hill C 2005 Smad4 dependency defines two classes of transforming growth factor β (TGF-β) target genes and distinguishes TGF-β-induced epithelial-mesenchymal transition from. Molecular and Cellular Biology 25 81088125. (https://doi.org/10.1128/MCB.25.18.8108)

    • Search Google Scholar
    • Export Citation
  • Minami S & Sarkar DK 1997 Transforming growth factor-beta 1 inhibits prolactin secretion and lactotropic cell proliferation in the pituitary of oestrogen-treated Fischer 344 rats. Neurochemistry International 30 499506. (https://doi.org/10.1016/s0197-0186(96)00087-3)

    • Search Google Scholar
    • Export Citation
  • Nazian SJ 1983 Pituitary function during the sexual maturation of the male rat: inhibition of prolactin secretion by exogenous dopamine. Biology of Reproduction 28 645651. (https://doi.org/10.1095/biolreprod28.3.645)

    • Search Google Scholar
    • Export Citation
  • Paez-Pereda M, Kuchenbauer F, Arzt E & Stalla GK 2005 Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix. Brazilian Journal of Medical and Biological Research 38 14871494. (https://doi.org/10.1590/S0100-879X2005001000005)

    • Search Google Scholar
    • Export Citation
  • Pastorcic M, De A, Boyadjieva N, Vale W & Sarkar DK 1995 Reduction in the expression and action of transforming growth factor beta 1 on lactotropes during estrogen-induced tumorigenesis in the anterior pituitary. Cancer Research 55 48924898.

    • Search Google Scholar
    • Export Citation
  • Perez PA, Petiti JP, Picech F, Guido CB, dV Sosa L, Grondona E, Mukdsi JH, De Paul AL, Torres AI & Gutierrez S 2018 Estrogen receptor beta regulates the tumoral suppressor PTEN to modulate pituitary cell growth. Journal of Cellular Physiology 233 14021413. (https://doi.org/10.1002/jcp.26025)

    • Search Google Scholar
    • Export Citation
  • Recouvreux MV, Guida MC, Rifkin DB, Becu-Villalobos D & Díaz-Torga G 2011 Active and total transforming growth factor-β1 are differentially regulated by dopamine and estradiol in the pituitary. Endocrinology 152 27222730. (https://doi.org/10.1210/en.2010-1464)

    • Search Google Scholar
    • Export Citation
  • Recouvreux MV, Camilletti MA, Rifkin DB, Becu-Villalobos D & Diaz-Torga G 2012 Thrombospondin-1 (TSP-1) analogs ABT-510 and ABT-898 inhibit prolactinoma growth and recover active pituitary transforming growth factor-beta1 (TGF-beta1). Endocrinology 153 38613871. (https://doi.org/10.1210/en.2012-1007)

    • Search Google Scholar
    • Export Citation
  • Recouvreux MV, Lapyckyj L, Camilletti MA, Guida MC, Ornstein A, Rifkin DB, Becu-Villalobos D & Diaz-Torga G 2013 Sex differences in the pituitary transforming growth factor-beta1 system: studies in a model of resistant prolactinomas. Endocrinology 154 41924205. (https://doi.org/10.1210/en.2013-1433)

    • Search Google Scholar
    • Export Citation
  • Recouvreux MV, Camilletti MA, Rifkin DB & Díaz-Torga G 2016 The pituitary TGFβ1 system as a novel target for the treatment of resistant prolactinomas. Journal of Endocrinology 228 R73R83. (https://doi.org/10.1530/JOE-15-0451)

    • Search Google Scholar
    • Export Citation
  • Recouvreux MV, Faraoni EY, Camilletti MA, Ratner L, Abeledo-Machado A, Rulli SB & Díaz-Torga G 2017 Sex differences in the pituitary TGFβ1 system: the role of TGFβ1 in prolactinoma development. Frontiers in Neuroendocrinology 50 118122. (https://doi.org/10.1016/j.yfrne.2017.10.003)

    • Search Google Scholar
    • Export Citation
  • Ribeiro SM, Poczatek M, Schultz-Cherry S, Villain M & Murphy-Ullrich JE 1999 The activation sequence of thrombospondin-1 interacts with the latency-associated peptide to regulate activation of latent transforming growth factor-beta. Journal of Biological Chemistry 274 1358613593. (https://doi.org/10.1074/jbc.274.19.13586)

    • Search Google Scholar
    • Export Citation
  • Rifkin DB 2005 Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta availability. Journal of Biological Chemistry 280 74097412. (https://doi.org/10.1074/jbc.R400029200)

    • Search Google Scholar
    • Export Citation
  • Sarkar DK, Kim KH & Minami S 1992 Transforming growth factor-beta 1 messenger RNA and protein expression in the pituitary gland: its action on prolactin secretion and lactotropic growth. Molecular Endocrinology 6 18251833. (https://doi.org/10.1210/mend.6.11.1480172)

    • Search Google Scholar
    • Export Citation
  • Sarkar DK, Pastorcic M, De A, Engel M, Moses H & Ghasemzadeh MB 1998 Role of transforming growth factor (TGF)-beta Type I and TGF-beta type II receptors in the TGF-beta1-regulated gene expression in pituitary prolactin-secreting lactotropes. Endocrinology 139 36203628. (https://doi.org/10.1210/endo.139.8.6135)

    • Search Google Scholar
    • Export Citation
  • Schultz-Cherry S, Ribeiro S, Gentry L & Murphy-Ullrich JE 1994 Thrombospondin binds and activates the small and large forms of latent transforming growth factor-β in a chemically defined system. Journal of Biological Chemistry 269 2677526782.

    • Search Google Scholar
    • Export Citation
  • Shi Y & Massague J 2003 Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113 685700. (https://doi.org/10.1016/s0092-8674(03)00432-x)

    • Search Google Scholar
    • Export Citation
  • Truty MJ, Lomberk G, Fernandez-Zapico ME & Urrutia R 2009 Silencing of the transforming growth factor-beta (TGFbeta) receptor II by Kruppel-like factor 14 underscores the importance of a negative feedback mechanism in TGFbeta signaling. Journal of Biological Chemistry 284 62916300. (https://doi.org/10.1074/jbc.M807791200)

    • Search Google Scholar
    • Export Citation
  • Walker DM, Kirson D, Perez LF & Gore AC 2012 Molecular profiling of postnatal development of the hypothalamus in female and male rats. Biology of Reproduction 87 129. (https://doi.org/10.1095/biolreprod.112.102798)

    • Search Google Scholar
    • Export Citation
  • Wrana JL 2013 Signaling by the TGFβ superfamily. Cold Spring Harbor Perspectives in Biology 5 a011197. (https://doi.org/10.1101/cshperspect.a011197)

    • Search Google Scholar
    • Export Citation
  • Yoshinaga K, Obata H, Jurukovski V, Mazzieri R, Chen Y, Zilberberg L, Huso D, Melamed J, Prijatelj P, Todorovic V, et al. 2008 Perturbation of transforming growth factor (TGF)-beta1 association with latent TGF-beta binding protein yields inflammation and tumors. PNAS 105 1875818763. (https://doi.org/10.1073/pnas.0805411105)

    • Search Google Scholar
    • Export Citation