ArticleAmerican journal of physiology. Endocrinology and metabolism2013
Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction.
Article in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 63 citations in OpenAlex.
- Case Report: rapid progressive puberty in siblings withFrontiers in endocrinology · 2026Article
- Angiotensin ATiScience · 2025Article
- The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis.The Journal of clinical investigation · 2023Article
- Agouti-related peptide neuronal silencing overcomes delayed puberty in neonatally underfed male mice.Journal of neuroendocrinology · 2022Article
- Reporting The Effects of Exposure to Monosodium Glutamate on The Regulatory Peptides of The Hypothalamic-Pituitary-Gonadal Axis.International journal of fertility & sterility · 2021Review
- Recent Advances in Hypertension: Intersection of Metabolic and Blood Pressure Regulatory Circuits in the Central Nervous System.Hypertension (Dallas, Tex. : 1979) · 2021Review
- Sirtuin (SIRT)-1: At the crossroads of puberty and metabolism.Current opinion in endocrine and metabolic research · 2020Article
- Single-Nucleus RNA Sequencing of the Hypothalamic Arcuate Nucleus of C57BL/6J Mice After Prolonged Diet-Induced Obesity.Hypertension (Dallas, Tex. : 1979) · 2020Article
- The Peripubertal Decline inJournal of the Endocrine Society · 2020Article
- PI3K signalling in leptin receptor cells: Role in growth and reproduction.Journal of neuroendocrinology · 2019Review
- Neuroanatomical Framework of the Metabolic Control of Reproduction.Physiological reviews · 2018Review
- Regulation of Hepatic Lipid Accumulation and Distribution by Agouti-Related Protein in Male Mice.Endocrinology · 2018Article
- Kisspeptin and Metabolism: The Brain and Beyond.Frontiers in endocrinology · 2018Review
- PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction.JCI insight · 2017Article
- Long-term consequences of obesity on female fertility and the health of the offspring.Current opinion in obstetrics & gynecology · 2017Review
- Intracerebroventricular injection of RFRP-3 delays puberty onset and stimulates growth hormone secretion in female rats.Reproductive biology and endocrinology : RB&E · 2017Article
- Leptin Signaling in AgRP Neurons Modulates Puberty Onset and Adult Fertility in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- The role of leptin in health and disease.Temperature (Austin, Tex.) · 2017Review
- Obese Neuronal PPARγ Knockout Mice Are Leptin Sensitive but Show Impaired Glucose Tolerance and Fertility.Endocrinology · 2017Article
- Defining a novel leptin-melanocortin-kisspeptin pathway involved in the metabolic control of puberty.Molecular metabolism · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4R in leptin receptor mutant (Lepr(db/db)) females result in restoration of fertility and lactation despite the persistence of obesity and insulin resistance. The overarching hypothesis in the present study is that the absence or reduction of leptin's inhibition of AGRP/NPY neurons leads to suppression of GnRH release in cases of leptin signaling deficiency. Since TAC2 (NKB)-TAC3R signaling plays a role in puberty maturation and is modulated by metabolic status, the other aim of this study is to test whether TAC2/NKB neurons in ARC regulated by melanocortinergic signals herein affect leptin's action on puberty and reproduction. Our data showed that AGRP deficiency in Lepr(db/db) females restores normal timing of vaginal opening and estrous cycling, although uterine weight gain and mammary gland development are morphologically delayed. Nonetheless, Agrp(-/-) Lepr(db/db) females are fertile and sustain adequate nutrition of pups with lactation to weaning age. AGRP deficiency results in advanced vaginal opening in wild-type female mice. The postpubertal increase in hypothalamic TAC2 mRNA was not observed in Lepr(db/db) females, whereas AGRP deficiency restored it in Lepr(db/db) females. Additionally, MC4R activation with MTII induced FOS expression in TAC2 neurons, supporting the concept of melanocortinergic regulation of TAC2 neurons. These studies suggest that AGRP imposes an inhibitory effect on puberty and that TAC2 neurons may transmit melanocortinergic inhibition of GnRH neurons.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.