Unraveling Hypothalamus-Pituitary dysregulation: Hypergonadotropism in F 1 progeny due to prenatal exposure to hexavalent chromium.

Autor: Navin AK; Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani-Velachery Link Road, Chennai, Tamil Nadu, India., Aruldhas MM; Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani-Velachery Link Road, Chennai, Tamil Nadu, India., Mani KK; Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani-Velachery Link Road, Chennai, Tamil Nadu, India., Navaneethabalakrishnan S; Department of Endocrinology, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani-Velachery Link Road, Chennai, Tamil Nadu, India., Venkatachalam S; Department of Anatomy, Dr. A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Taramani-Velachery Link Road, Chennai, Tamil Nadu, India., Banu SK; Department of Veterinary Integrative Biosciences, College of Veterinary Medicine & Biomedical Sciences, TAMU-4458, Texas A&M University, College Station, TX, USA.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2024 Apr; Vol. 38 (4), pp. e23699.
DOI: 10.1002/jbt.23699
Abstrakt: The endocrine disruptor hexavalent chromium [Cr(VI)] is a proven reproductive toxicant. We recently demonstrated that prenatal Cr(VI) exposure causes testicular resistance to gonadotropins, resulting in hypergonadotropic hypoandrogenism in F 1 rats. However, the mechanism driving hypergonadotropism in F 1 rats exposed to Cr(VI) prenatally remains an enigma. Therefore, we hypothesized that 'Prenatal Cr(VI) exposure may disrupt steroid hormones-mediated negative feedback regulation of the hypothalamic GnRH, and its receptor in the pituitary of F1 rats, leading to hypergonadotropism.' We administered potassium dichromate (50, 100, or 200 mg/L) to pregnant rats through drinking water between days 9 and 14, and their male F1 offspring were euthanized at 60 days of age. Prenatal Cr(VI) exposure in F 1 rats resulted in the accumulation of Cr in the hypothalamus and pituitary. Western blot detected decreased hypothalamic GnRH, Kisspeptin1, and its receptor GPR54, along with diminished ERα, AR, aromatase, and 5α reductase, and GnRH regulatory transcription factors Pit-1 and GATA-4 proteins. Immunohistochemical studies revealed increased immunopositivity of GnRH receptor, AR, 5α reductase, ERα, ERβ, and aromatase proteins in the pituitary, whereas decreased Kisspeptin1, GPR54, and inhibin β. Our findings imply that Cr(VI) exposure during the prenatal period disrupts the hypothalamic Kisspeptin-GPR54-Pit-1/GATA4-GnRH network, boosting the pituitary GnRH receptor. We conclude that prenatal exposure to Cr(VI) alters GnRH expression in the hypothalamus and its receptor in the pituitary of F1 progeny through interfering with the negative feedback effect of androgens and estrogens.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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