Persistently expressed human chorionic gonadotropin induces premature luteinization and progressive alterations on the reproductive axis in female mice.

Autor: Marcial Lopez A; Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490 (1428), Buenos Aires, Argentina., Ratner LD; Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490 (1428), Buenos Aires, Argentina., Martinez CS; Laboratorio de Bio-nanotecnología, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Grupo vinculado GBEyB, IMBICE-CONICET-CICPBA, Bernal, Argentina., Di Giorgio N; Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490 (1428), Buenos Aires, Argentina., Poutanen M; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Turku Center for Disease Modeling, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland., Huhtaniemi IT; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland; Department of Metabolism, Digestion and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London, London W12 0NN, UK., Rulli SB; Instituto de Biología y Medicina Experimental-CONICET, Vuelta de Obligado 2490 (1428), Buenos Aires, Argentina. Electronic address: rulli.susana@maimonides.edu.
Jazyk: angličtina
Zdroj: General and comparative endocrinology [Gen Comp Endocrinol] 2023 May 15; Vol. 336, pp. 114247. Date of Electronic Publication: 2023 Feb 27.
DOI: 10.1016/j.ygcen.2023.114247
Abstrakt: The hypothalamic-pituitary-gonadal axis plays a fundamental role in the endocrine regulation of the reproductive function in mammals. Any change in the function of the participating hormones or their receptors can lead to alterations in sexual differentiation, the onset of puberty, infertility, cancer development, and other dysfunctions. In this study, we analyzed the influence of persistently elevated levels of the human chorionic gonadotropin hormone (hCG), a powerful agonist of pituitary luteinizing hormone (LH), on the reproductive axis of female mice. As a consequence of chronic hCG hypersecretion through a global expression of the hCGbeta-subunit in transgenic (TG) female mice, a series of events perturbed the prepubertal to juvenile transition. The imbalance in gonadotropin action was first manifested by precocious puberty and alterations in gonadal hormone production, with the consequent ovarian function disruption and infertility in adulthood. The expansion of cumulus cells in vivo and in vitro, ovulatory capacity, and gene expression of ovulation-related marker genes after hormone stimulation were normal in 3-week-old TG females. However, the expression of genes related to steroidogenesis and luteinization such as Lhcgr, Prlr, and the steroidogenic enzymes Cyp11a1, Cyp17a1, and Cyp19a1 were significantly elevated in the TG females. This study demonstrates that the excessive secretion of hCG in concert with high prolactin, induced premature luteinization, and enhanced ovarian steroidogenesis, as was shown by the up-regulation of luteal cell markers and progesterone synthesis in the TG mice. Furthermore, progressively impaired reproductive function of the TG females occurred from the peripubertal stage to adulthood, thus culminating in infertility.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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