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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Distinct effects of growth hormone deficiency and disruption of hypothalamic kisspeptin system on reproduction of male mice

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Paula, Daniella G. de [1] ; Bohlen, Tabata M. [1] ; Zampieri, Thais Tessari [1] ; Mansano, Naira S. [1] ; Vieira, Henrique R. [1] ; Gusmao, Daniela O. [2] ; Wasinski, Frederick [2] ; Donato Jr, Jose ; Frazao, Renata [1]
Total Authors: 9
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, Av Prof Lineu Prestes 2415, Room 108, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Life Sciences; v. 285, NOV 15 2021.
Web of Science Citations: 0

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 (Ghrhr(lit/lit) mice). Interestingly, although Ghrhr(lit/lit) mice exhibited late puberty onset, hypothalamic Kiss1 mRNA expression and hypothalamic kisspeptin fiber density were normal in Ghrhr(lit/lit) mice. Despite presenting dwarfism, the majority of Ghrhr(lit/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. (AU)

FAPESP's process: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions
Grantee:Jose Donato Junior
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/03082-6 - Effects of monosodium glutamate administration in Kiss1 neurons and its correlation with reproductive disorders
Grantee:Daniella Gonçalves de Paula
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 21/03316-5 - Evaluation of the importance of GABAergic and dopaminergic transmission in neurons that express the growth hormone-releasing hormone to the control of GH secretion
Grantee:Daniela de Oliveira Gusmão
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/20897-3 - Role of orexin neurons as mediators of the central effects induced by growth hormone
Grantee:Frederick Wasinski
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/20198-5 - Role of Leptin in puberal neuromodulation
Grantee:Thais Tessari Zampieri
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/07908-8 - Precocious puberty in childhood obesity: possible mechanisms and influence of leptin
Grantee:Renata Frazão
Support Opportunities: Regular Research Grants
FAPESP's process: 15/14588-5 - Influence of leptin sensitivity in mice sexual maturation
Grantee:Tabata Mariz Bohlen
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 17/22189-9 - Does the factors that change food intake modulate the activity of Kiss1 neurons?
Grantee:Naira da Silva Mansano
Support Opportunities: Scholarships in Brazil - Doctorate