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1.
Cytokine ; 158: 155999, 2022 10.
Article in English | MEDLINE | ID: mdl-35985175

ABSTRACT

Many cytokines have been proposed to regulate reproduction due to their actions on hypothalamic kisspeptin cells, the main modulators of gonadotropin-releasing hormone (GnRH) neurons. Hormones such as leptin, prolactin and growth hormone are good examples of cytokines that lead to Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation, consequently exerting effects in kisspeptin neurons. Different studies have investigated how specific components of the JAK/STAT signaling pathway affect the functions of kisspeptin cells, but the role of the suppressor of cytokine signaling 3 (SOCS3) in mediating cytokine actions in kisspeptin cells remains unknown. Cre-Loxp technology was used in the present study to ablate Socs3 expression in kisspeptin cells (Kiss1/Socs3-KO). Then, male and female control and Kiss1/Socs3-KO mice were evaluated for sexual maturation, energy homeostasis features, and fertility. It was found that hypothalamic Kiss1 mRNA expression is significantly downregulated in Kiss1/Socs3-KO mice. Despite reduced hypothalamic Kiss1 mRNA content, these mice did not present any sexual maturation or fertility impairments. Additionally, body weight gain, leptin sensitivity and glucose homeostasis were similar to control mice. Interestingly, Kiss1/Socs3-KO mice were partially protected against lipopolysaccharide (LPS)-induced body weight loss. Our results suggest that Socs3 ablation in kisspeptin cells partially prevents the sickness behavior induced by LPS, suggesting that kisspeptin cells can modulate energy metabolism in mice in certain situations.


Subject(s)
Kisspeptins , Lipopolysaccharides , Animals , Body Weight/physiology , Cytokines/metabolism , Female , Kisspeptins/genetics , Kisspeptins/metabolism , Leptin/metabolism , Lipopolysaccharides/pharmacology , Male , Mice , RNA, Messenger , Suppressor of Cytokine Signaling 3 Protein/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolism , Weight Loss
2.
Life Sci ; 194: 157-167, 2018 Feb 01.
Article in English | MEDLINE | ID: mdl-29287783

ABSTRACT

AIMS: To analyze the effects of radiation on the reproductive tissue of male Wistar rats and to evaluate whether treatment with the Ang II AT1 receptor antagonists telmisartan and losartan mitigate the dysfunctions resulting from this exposure. MAIN METHODS: Rats were randomly divided into groups: Control, Irradiated, Telmisartan, Losartan, Irradiated+Telmisartan, and Irradiated+Losartan. Single dose of 5Gy was administered directly into the scrotum, followed by treatment with telmisartan (12mg/kg/day) or losartan (34mg/kg/two times/day) for 60days. Testicular function parameters were evaluated from spermatozoa of the vas deferens. Testes were processed for histopathological and morphometric-stereological analysis. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was evaluated. KEY FINDINGS: Radiation significantly reduced sperm motility, concentration, vitality, and increased the number of abnormal spermatozoa. Telmisartan and losartan did not significantly prevent these radiation-induced disorders. Seminiferous tubules were atrophied in both untreated and treated irradiated testes, and exhibited vacuoles, increased interstitial tissue and high number of blood vessels. However, several seminiferous tubules in recuperation were founded among damaged tubules in the testes of treated animals. The PCNA immunohistochemistry confirmed these outcomes. PCNA-positive cells were detected in dividing spermatogonia and spermatocytes from irradiated telmisartan and losartan treated rats whereas in the only-irradiated group, PCNA staining was observed in the nuclei of only the surviving spermatogonia. SIGNIFICANCE: Under these experimental conditions, the testicular function parameters showed that radiation produced marked damage that was not reversed by treatments. However, gonadal restructuring and recovery of spermatogenesis in treated animals may to reflect attenuation of radiation-induced damages and potential start of recovery.


Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/pharmacology , Benzoates/pharmacology , Losartan/pharmacology , Radiation-Protective Agents/pharmacology , Testis/drug effects , Testis/radiation effects , Animals , Male , Rats, Wistar , Spermatogenesis/drug effects , Spermatogenesis/radiation effects , Spermatozoa/drug effects , Spermatozoa/pathology , Spermatozoa/radiation effects , Telmisartan , Testis/pathology , Testis/physiopathology
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