Distinct effects of growth hormone deficiency and disruption of hypothalamic kisspeptin system on reproduction of male mice
Autor: | Daniela O. Gusmao, Henrique Rodrigues Vieira, Thais T. Zampieri, Jose Donato, Tabata Mariz Bohlen, Daniella G. de Paula, Renata Frazão, Naira da Silva Mansano, Frederick Wasinski |
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Rok vydání: | 2021 |
Předmět: |
Male
Receptors Neuropeptide Infertility Hypothalamo-Hypophyseal System medicine.medical_specialty Monosodium glutamate Dwarfism Biology General Biochemistry Genetics and Molecular Biology Growth hormone deficiency Mice chemistry.chemical_compound Kisspeptin Receptors Pituitary Hormone-Regulating Hormone Arcuate nucleus Internal medicine medicine Animals Sexual maturity Sexual Maturation General Pharmacology Toxicology and Pharmaceutics SISTEMA HIPOTÁLAMO-HIPOFISÁRIO Neurons Kisspeptins Reproduction Arcuate Nucleus of Hypothalamus General Medicine medicine.disease Fertility Endocrinology chemistry Hypothalamus Growth Hormone |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
Popis: | Growth hormone (GH) deficiency is a common cause of late sexual maturation and fertility issues. To determine whether GH-induced effects on reproduction are associated with alterations in hypothalamic kisspeptin system, we studied the male reproduction in two distinct GH deficiency mouse models. In the first model, mice present GH deficiency secondary to arcuate nucleus of the hypothalamus (ARH) lesions induced by posnatal monosodium glutamate (MSG) injections. MSG-induced ARH lesions led to significant reductions in hypothalamic Ghrh mRNA expression and consequently growth. Hypothalamic Kiss1 mRNA expression and Kiss1-expressing cells in the ARH were disrupted in the MSG-treated mice. In contrast, kisspeptin immunoreactivity remained preserved in the anteroventral periventricular and rostral periventricular nuclei (AVPV/PeN) of MSG-treated mice. Importantly, ARH lesions caused late sexual maturation and infertility in male mice. In our second mouse model, we studied animals profound GH deficiency due to a loss-of-function mutation in the Ghrhr gene (Ghrhrlit/lit mice). Interestingly, although Ghrhrlit/lit mice exhibited late puberty onset, hypothalamic Kiss1 mRNA expression and hypothalamic kisspeptin fiber density were normal in Ghrhrlit/lit mice. Despite presenting dwarfism, the majority of Ghrhrlit/lit male mice were fertile. These findings suggest that spontaneous GH deficiency during development does not compromise the kisspeptin system. Furthermore, ARH Kiss1-expressing neurons are required for fertility, while AVPV/PeN kisspeptin expression is sufficient to allow maturation of the hypothalamic-pituitary-gonadal axis in male mice. |
Databáze: | OpenAIRE |
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