Hypothalamic regulation

The hypothalamic neuropeptides modulate physiological activity via G pro-tein-coupled receptors (GPCRs). Galanin-like peptide (GALP) is a 60 amino acid neuropeptide that was originally isolated from porcine hypo-thalamus using a binding assay for galanin receptors, which belong to the GPCR family.

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We are very pleased to launch the 23rd edition of Ganong's Review of Medical Physiology . The current authors have attempted to maintain the highest standards of excellence, accuracy, and pedagogy developed by Fran Ganong over the 46 years in which he educated countless students worldwide with this textbook. At the same time, we have been attuned to the evolving needs of both students and professors in medical physiology.

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Metabolic integration of nutrient sensing in the central nervous system has been shown to be an important regulator of adiposity by affecting food intake and peripheral energy expenditure. Modulation of de novofatty acid synthetic flux by cytokines and nutrient availability plays an important role in this process.

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Gonadotropin-releasing hormone (GnRH) I and II are hypothalamic deca-peptides with pivotal roles in the development of reproductive competence and regulation of reproductive events. In this study, transcriptional regula-tion of the human GnRH IIgene was investigated.

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The peptide hormones of the anterior pituitary are essential for the regulation of growth and development, reproduction, responses to stress, and intermediary metabolism. Their synthesis and secretion are controlled by hypothalamic hormones and by hormones from the peripheral endocrine organs. A large number of disease states as well as a diverse group of drugs also affect their secretion.

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The Hypothalamushypophysis- gonadal (HPG) axis is subject to both positive feed-forward and negative feedback regulation at several levels. At the level of the hypothalamus, early recognition of the pulsatile nature of gonadotropin releasing hormone secretion led to the notion of a central ‘‘pulse generator”, the inherent oscillatory activity of which controls the secretory rhythm of GnRH neurons (Knobil, 1980).

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Role of the hypothalamic-pituitary-gonadal axis in the etiology of amenorrhea. Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion from the pituitary to induce ovarian folliculogenesis and steroidogenesis. Ovarian secretion of estradiol and progesterone controls the shedding of the endometrium, resulting in menses and, in combination with the inhibins, provides feedback regulation of the hypothalamus and pituitary to control secretion of FSH and LH.

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A central pathway through which leptin acts to regulate appetite and body weight. Leptin signals through proopiomelanocortin (POMC) neurons in the hypothalamus to induce increased production of α-melanocyte-stimulating hormone (α-MSH), requiring the processing enzyme PC-1 (proenzyme convertase 1). α-MSH acts as an agonist on melanocortin-4 receptors to inhibit appetite, and the neuropeptide AgRp (Agouti-related peptide) acts as an antagonist of this receptor. Mutations that cause obesity in humans are indicated by the solid green arrows.

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Because of the physiologic importance of maintaining energy stores, voluntary weight loss is difficult to achieve and sustain.Appetite and metabolism are regulated by an intricate network of neural and hormonal factors. The hypothalamic feeding and satiety centers play a central role in these processes (Chap. 74). Neuropeptides such as corticotropin-releasing hormone (CRH), α-melanocyte-stimulating hormone (α-MSH), and cocaine- and amphetamine-related transcript (CART) induce anorexia by acting centrally on satiety centers.

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