REVIEW ARTICLE Anatomy of the Hypophysiotropic Somatostatinergic and Growth Hormone-releasing Hormone System Minireview Mariann Fodor Æ Claude Kordon Æ Jacques Epelbaum Accepted: 31 October 2005 / Published online: 4 April 2006 Ó Springer Science+Business Media, Inc. 2006 Abstract The central control of growth hormone (GH) secretion from the pituitary gland is ultimately achieved by the interaction between two hypothalamic neurohormones, somatostatin which inhibits and growth hormone-releasing hormone (GHRH) which stimulates GH release. The reg- ulation of the somatostatin and GHRH release from the hypothalamus is regulated by a range of other neuropep- tides, neurotransmitters, neurohormones. In this mini re- view we attempt to provide a short summary covering the anatomy and chemical characteristics of the various cell populations regulating GH secretion as a tribute to Miklo ´s Palkovits who pioneered the field of functional neuro- anatomy of hypothalamic networks. Keywords Hypothalamus Æ Somatostatin Æ Growth hormone-releasing hormone Æ Colocalization Æ CART Æ Ghrelin The ultradian pulsatility of plasma growth hormone (GH) levels is based on the rhythmic secretion patterns of two antagonistic neurohormonal neuronal systems: somato- statin and GH-releasing hormone (GHRH). However, the release of GH is controlled by a wide range of other neu- rotransmitters and neuropeptides. In rats, GH pulsatility is intrinsic to the hypothalamus since animals with a com- pletely deafferented hypothalamus still able to maintain episodic secretion [1]. Somatostatin neurons projecting to the median eminence are located within the rostral peri- ventricular nucleus and the parvocellular paraventricular nucleus [2–4] while hypophysiotropic GHRH neurons are confined to the ventrolateral part of the arcuate nucleus [5, 6] (Fig. 1). Other somatostatin cell bodies and fibers are scattered throughout hypothalamic regions such as the suprachiasmatic, arcuate, ventromedial and dorsomedial nuclei [7] while GHRH immunoreactive neurons are only located in the arcuate nucleus and around the rim of the ventromedial nucleus [8] (Fig. 1). Numerous ultrastructural evidences exist for bidirec- tional synaptic connections between GHRH- and somato- statin-containing hypophysiotrophic neurons [9, 10]. We have been among the first to characterize somatostatin receptors on a majority of GHRH neurons of the ventro- lateral arcuate population of GHRH mRNA-containing neurons [11]. Somatostatin receptors are also visualized on several GHRH immunoreactive cells in that region [12]. After cloning selective membrane receptors (sst1–5) mediating the effect of somatostatin at both pituitary and/or hypothalamic level (for rev. see [13]) it also appeared that 15% of GHRH neurons contained sst1 or sst2 [14]. Special Issue Dedicated to Miklo ´s Palkovits. M. Fodor Department of Pediatrics, VU University Medical Center, Amsterdam, The Netherlands M. Fodor Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands C. Kordon Institut Necker, Paris, France J. Epelbaum INSERM-Universite ´ Paris 5 UMR, 549 Paris, France M. Fodor (&) Department of Anatomy and Embryology, Leiden University Medical Center, 9602, 2300 RC Leiden, The Netherlands E-mail: M.Fodor@lumc.nl Tel.: +31-71-527-66-60 Fax: +31-71-527-66-80 Neurochem Res (2006) 31:137–143 DOI 10.1007/s11064-005-9017-3 123