Kisspeptin and galanin-like peptide (GALP) neurons in the hypothalamic arcuate nucleus (ARC) are involved in gonadotropin-releasing hormone (GnRH) neuron-mediated pulsatile luteinizing hormone (LH) secretion. Zucker fatty (ZF) rats display a leptin receptor gene abnormality and suppressed pulsatile LH secretion. ZF rats reportedly exhibit low hypothalamic GALP and kisspeptin expression, and GALP administration induces LH release in ZF rats.
View Article and Find Full Text PDFDiabetes mellitus disturbs kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the arcuate nucleus (ARC), which regulate pulsatile luteinizing hormone (LH) secretion in both sexes. However, it remains unclear whether a sex-specific association with the negative effects of diabetes on KNDy neurons exists. Therefore, we examined mRNA expression in KNDy neurons of diabetic male and female rats 7 weeks after streptozotocin (STZ) injection using histochemistry.
View Article and Find Full Text PDFIntroduction: Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA).
Methods: Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing.
Macrophages are essential for the proper inflammatory and reparative processes that lead to regeneration of skeletal muscle after injury. Recent studies have demonstrated close links between the function of activated macrophages and their cellular metabolism. Sterol regulatory element-binding protein 1 (SREBP1) is a key regulator of lipid metabolism and has been shown to affect the activated states of macrophages.
View Article and Find Full Text PDFMammalian ovulation is induced by a luteinizing hormone surge, which is triggered by elevated plasma estrogen levels; however, chronic exposure to high levels of estradiol is known to inhibit luteinizing hormone secretion. In the present study, we hypothesized that the inhibition of the luteinizing hormone surge by chronic estradiol exposure is due to the downregulation of the estrogen receptor alpha in kisspeptin neurons at hypothalamic anteroventral periventricular nucleus, which is known as the gonadotropin-releasing hormone/luteinizing hormone surge generator. Animals exposed to estradiol for 2 days showed an luteinizing hormone surge, whereas those exposed for 14 days showed a significant suppression of luteinizing hormone.
View Article and Find Full Text PDFJ Nippon Med Sch
November 2023
Estrogen receptor α (ERα) regulates several physiological functions. In pathophysiological conditions, ERα is involved in the development and progression of estrogen-sensitive tumors. The ERα gene contains multiple 5'-untranslated exons and eight conventional coding exons and presents multiple isoforms generated by alternative promoter usage and alternative splicing.
View Article and Find Full Text PDFNeuropeptide B (NPB) has been identified as an endogenous peptide ligand for the orphan receptor NPBWR1. However, the effect of NPB on the central regulatory mechanisms of reproductive functions remains unclear. Our findings indicated the presence of Npb, Npw (which is another ligand for NPBWR1), and Npbwr1 mRNA in the hypothalamus of male and female rats at each stage of the estrous cycle.
View Article and Find Full Text PDFhybridization (ISH), which visualizes nucleic acids in tissues and cells, is a powerful tool in histology and pathology. Over 50 years since its invention, multiple attempts have been made to increase the sensitivity and simplicity of these methods. Therefore, several highly sensitive hybridization methods have been developed that offer researchers a wide range of options.
View Article and Find Full Text PDFKisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the arcuate nucleus (ARC) regulate pulsatile luteinizing hormone (LH) secretion. These neurons express estrogen receptors and are negatively regulated by estrogen. This study aimed to determine whether estrogen supplementation after short-term ovariectomy-induced estrogen depletion has different effects on KNDy neurons depending on the timing of the supplementation.
View Article and Find Full Text PDFThe nutritional environment during development periods induces metabolic programming, leading to metabolic disorders and detrimental influences on human reproductive health. This study aimed to determine the long-term adverse effect of intrauterine malnutrition on the reproductive center kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus (ARC) of female offspring. Twelve pregnant rats were divided into ad-lib-fed (control, n = 6) and 50% undernutrition (UN, n = 6) groups.
View Article and Find Full Text PDFNat Rev Endocrinol
September 2022
The suprachiasmatic nucleus (SCN) of the hypothalamus is a nucleus that regulates circadian rhythms through the cyclic expression of clock genes. It has been suggested that circadian-rhythm-related, adverse postoperative events, including sleep disturbances and delirium, are partly caused by anesthesia-induced disruption of clock-gene expression. We examined the effects of multiple general anesthetics on the expression cycle of Period2 (Per2), one of the clock genes that regulate circadian rhythms in the SCN, and on the behavioral rhythms of animals.
View Article and Find Full Text PDFKisspeptin neurons, i.e. KNDy neurons, in the arcuate nucleus (ARC) coexpress neurokinin B and dynorphin and regulate gonadotropin-releasing hormone/luteinizing hormone (LH) pulses.
View Article and Find Full Text PDFBackground: Regulation of the reproductive system has been explained by the actions and feedback of gonadotropin releasing hormone-luteinizing hormone/follicle stimulating hormone (GnRH-LH/FSH) -sex steroids; however, the discovery of kisspeptin neurons and a kisspeptin-GnRH-LH/FSH axis has prompted this regulation to be reviewed.
Methods: We investigated changes in kisspeptin neurons and associated changes in the hypothalamic-pituitary-gonadal (HPG) axis under various situations and experimental conditions using histochemical methods.
Main Findings Results: Kisspeptin neurons play an important role in receiving and integrating information from internal and external environmental factors and communicating it to the conventional HPG axis.
Background: The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders.
View Article and Find Full Text PDFCesarean section (C/S) is one way of delivering babies, and is chosen when mothers or babies are facing problems or life-threatening conditions during pregnancy. Many meta-analyses have suggested an etiological relationship between C/S delivery and autism spectrum disorders (ASDs). However, as a risk factor for ASDs, C/S delivery has not yet been well studied.
View Article and Find Full Text PDFMetabolic stress resulting from either lack or excess of nutrients often causes infertility in both sexes. Kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the arcuate nucleus (ARC) has been suggested to be a key players in reproduction via direct stimulation of the pulsatile gonadotropin-releasing hormone (GnRH) and subsequent gonadotropin release in mammalian species. In this study, we investigated the effect of high-fat diet (HFD) on hypothalamic KNDy gene expression to examine the pathogenic mechanism underlying obesity-induced infertility in male and female rats.
View Article and Find Full Text PDF