Role of leptin in hypothalamic–pituitary function

Yu, Wen H.; Kimura, Mayumi; Walczewska, Anna; Karanth, Sharada; McCann, Samuel M.

doi:10.1073/pnas.94.3.1023

Cited by 667 publications

(504 citation statements)

References 34 publications

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“…Leptin increased LH levels in ovariectomized, estrogen-primed rats [72,73]. Antiserum to leptin suppressed LH secretion and disrupted the estrous cycles [160].…”

Section: Pituitary Leptin and Paracrine Interac-tionsmentioning

confidence: 96%

“…Third, more specific paracrine role for pituitary leptin is suggested by the collective evidence showing that leptin is known to be a secretagogue for LH, both in vivo and in vitro [67,70,73,74,120]. There is no rapid periovulatory rise in serum leptin coming from adipocytes to permit or facilitate an LH surge.…”

Section: Changes In Pituitary Leptin Expression With the Reproductivementioning

confidence: 99%

“…Interestingly, no changes were noted in hypothalamic GHRH levels themselves, which suggested that GHRH did not mediate the restoration. In addition, several in vitro studies showed that leptin directly stimulated LH secretion [70][71][72][73][74] and may stimulate or inhibit GH [23,68,76,77,79,80,88,114,[179][180][181][182][183][184], depending on experimental conditions. In light of these findings, we hypothesized that, if it was a paracrine regulator, pituitary leptin might itself be regulated by the nutrient status.…”

Section: Pituitary Leptin and Paracrine Interac-tionsmentioning

confidence: 99%

“…Leptin also restores LH secretion in fasted mice, rats, hamsters and monkeys [14-17, 20, 58, 64, 67, 68]. Leptin also directly stimulates LH secretion from pituitary cells in vitro [70][71][72][73][74]. In addition, leptin regulates Growth hormone (GH) [19], although there is lack of agreement about the exact direction of its regulation [19,[75][76][77][78].…”

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confidence: 99%

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Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

2011

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Leptin, a potent anorexigenic hormone secreted primarily by adipocytes, is known to be expressed in the anterior pituitary. Studies in our laboratory found leptin proteins and mRNA predominantly in somatotropes in normal male and cycling female rats. In contrast, leptin expression predominated in gonadotropes during pregnancy and lactation. Leptin expression varied with the cycle and was enhanced, in vitro by gonadotropin releasing hormone and Neuropeptide Y. In contrast, ghrelin inhibited pituitary leptin expression. Pituitary leptin in somatotropes or gonadotropes was reduced by nutritional deprivation for 24 h. However, growth hormone (GH), luteinizing hormone (LH) and pituitary leptin recovered if fasted animals were given glucose water. The glucose-mediated recovery suggests that the system is sensitive to changes in serum glucose. Somatotropes and gonadotropes also recovered if pituitary cells from fasted rats were stimulated in vitro with 1-100 pg/ml leptin. This in vitro leptin-mediated recovery suggests that leptin is important in the maintenance of somaotropes and gonadotropes. Collectively, the data suggest that pituitary leptin might serve as a "glucostat", sensing levels of serum glucose and reporting this nutritional state to somaotropes and gonadotropes in a paracrine manner. A decrease in pituitary leptin might signal nutritional deprivation to somatotropes and gonadotropes, lowering LH and GH production and allowing for conservation of resources. Lower GH would help conserve fat stores and lower LH would promote survival over reproduction.

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“…Leptin increased LH levels in ovariectomized, estrogen-primed rats [72,73]. Antiserum to leptin suppressed LH secretion and disrupted the estrous cycles [160].…”

Section: Pituitary Leptin and Paracrine Interac-tionsmentioning

confidence: 96%

Section: Changes In Pituitary Leptin Expression With the Reproductivementioning

confidence: 99%

Section: Pituitary Leptin and Paracrine Interac-tionsmentioning

confidence: 99%

mentioning

confidence: 99%

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Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

2011

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“…Estudos em camundongos revelaram que a leptina age no eixo HHG centralmente estimulando a liberação de LH e FSH da hipófise (28)…”

Section: Genes No Eixo Hipotálamo-hipófise-gonadalunclassified

Genética molecular do eixo hipotálamo-hipófise-gonadal

Costa

Domenice

Corrêa

et al. 2003

Arq Bras Endocrinol Metab

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RESUMONessa revisão, descrevemos os genes que codificam uma rede de fatores de transcrição, proteínas, hormônios, enzimas e receptores expressos nos diversos níveis do eixo hipotálamo-hipófise-gonadal (HHG), e relatamos nossa experiência na identificação e caracterização das mutações identificadas em pacientes com alterações do eixo HHG, incluindo o hipogonadismo hipergonadotrófico e o hipogonadismo hipogonadotrófico isolado ou associado a outras deficiências hormonais hipofisárias, e alterações do desenvolvimento puberal e sexual. Até o momento, foram identificados 15 genes que atuam no desenvolvimento e função do eixo HHG: KAL, SF1, DAX1, LEPTINA, PC1, GnRH, GnRHR, HESX1, LHX3, PROP1, FSHR, LHR, FSHβ, LHβ e FGFR1. A maioria das mutações identificadas em nossa casuística foi descrita pela primeira vez na literatura e freqüentemente esteve associada a novos aspectos clínicos e hormonais das doenças. As conseqüências dessas mutações, caracterizadas por estudos in vitro, contribuíram para um melhor entendimento da estrutura e função das proteínas codificadas por esses genes. A união do diagnóstico clínico, hormonal e molecular dos distúr-bios do eixo HHG contribui significantemente para aprimorar o conhecimento e, conseqüentemente, o diagnóstico e a terapêutica destes pacientes. In this review, we described the genes that encode an array of transcription factors, matrix proteins, hormones, enzymes and receptors that are expressed at multiple levels of the hypothalamic-pituitary-gonadal axis (HPG). In addition, we reported our experience in the identification and characterization of naturally occurring mutations in patients affected by HPG disorders, including hypergonadotropic hypogonadism and hypogonadotropic hypogonadism, isolated or associated with others pituitary hormonal deficiencies, and abnormalities of pubertal and sexual development. To date, fifteen distinct genes implicated with HPG axis development and function were identified: KAL, SF1, DAX1, LEPTIN, PC1, GnRH, GnRHR, HESX1, LHX3, PROP1, FSHR, LHR, LHβ, FSHβ and FGFR1. Most mutations identified in our cohort were described for the first time in literature and they frequently were associated with new clinical and hormonal aspects of the diseases. Characterization of the consequences of these mutations in in vitro studies have provided increased understanding of the structure and function of the proteins encoded by these genes. The combined clinical, hormonal and molecular diagnosis of HPG disorders have helped significantly to improve the knowledge and, consequently, the diagnosis and treatment of these patients.

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