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Feedback Regulation of Growth Hormone Synthesis and Secretion in Fish and the Emerging Concept of Intrapituitary Feedback Loop ☆ ⁎ Anderson O.L

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Feedback Regulation of Growth Hormone Synthesis and Secretion in Fish and the Emerging Concept of Intrapituitary Feedback Loop ☆ ⁎ Anderson O.L http://www.paper.edu.cn Comparative Biochemistry and Physiology, Part A 144 (2006) 284–305 Review Feedback regulation of growth hormone synthesis and secretion in fish and the emerging concept of intrapituitary feedback loop ☆ ⁎ Anderson O.L. Wong , Hong Zhou, Yonghua Jiang, Wendy K.W. Ko Department of Zoology, University of Hong Kong, Pokfulam Road, Hong Kong, P.R. China Received 29 July 2005; received in revised form 21 November 2005; accepted 21 November 2005 Available online 9 January 2006 Abstract Growth hormone (GH) is known to play a key role in the regulation of body growth and metabolism. Similar to mammals, GH secretion in fish is under the control of hypothalamic factors. Besides, signals generated within the pituitary and/or from peripheral tissues/organs can also exert a feedback control on GH release by effects acting on both the hypothalamus and/or anterior pituitary. Among these feedback signals, the functional role of IGF is well conserved from fish to mammals. In contrast, the effects of steroids and thyroid hormones are more variable and appear to be species-specific. Recently, a novel intrapituitary feedback loop regulating GH release and GH gene expression has been identified in fish. This feedback loop has three functional components: (i) LH induction of GH release from somatotrophs, (ii) amplification of GH secretion by GH autoregulation in somatotrophs, and (iii) GH feedback inhibition of LH release from neighboring gonadotrophs. In this article, the mechanisms for feedback control of GH synthesis and secretion are reviewed and functional implications of this local feedback loop are discussed. This intrapituitary feedback loop may represent a new facet of pituitary research with potential applications in aquaculture and clinical studies. © 2005 Elsevier Inc. All rights reserved. Keywords: Growth hormone; Luteinizing hormone; Feedback control; Gene expression; Autocrine/paracrine interactions; Gonadotrophs; Somatotrophs; Signal transduction; Pituitary; Fish Contents 1. Introduction .............................................................. 284 2. Feedback regulation of GH synthesis and secretion in mammals ................................... 285 3. Feedback regulation of GH synthesis and secretion in fish ...................................... 288 4. Intrapituitary feedback loop for GH regulation in fish model ..................................... 293 5. Conclusion............................................................... 297 Acknowledgements ............................................................. 298 References ................................................................. 298 ☆ From the Symposium “Comparative Neuroendocrinology—Integration of 1. Introduction Hormonal and Environmental Signals in Vertebrates and Invertebrates” presented at the 15th International Congress of Comparative Endocrinology, Growth hormone (GH) is an important pituitary hormone May 23–28, 2005, at Boston, MA, USA (Organizer: Dr. Vance Trudeau, known to regulate body growth and metabolism. In University of Ottawa, Canada). mammals, GH release is under the control of hypothalamic ⁎ Corresponding author. Room 4S-12, Kadoorie Biological Sciences Building, Department of Zoology, University of Hong Kong, Pokfulam Road, Hong regulators, hormones released from target organs/peripheral Kong, P.R. China. Tel.: +852 2299 0863; fax: +852 2299 9114. tissues, feedback regulation by GH itself, and growth E-mail address: [email protected] (A.O.L. Wong). factors/cytokines produced locally within the pituitary 1095-6433/$ - see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.cbpa.2005.11.021 转载 中国科技论文在线 http://www.paper.edu.cn A.O.L. Wong et al. / Comparative Biochemistry and Physiology, Part A 144 (2006) 284–305 285 (Bluet-Pajot et al., 1998; McMahon et al., 2001; Muller et 2. Feedback regulation of GH synthesis and secretion in al., 1999). There is also increasing evidence suggesting that mammals local interactions among pituitary cells via the release of pituitary hormones can modulate the secretory functions in In mammals, GH release is under the dual control of GH- somatotrophs (Schwartz, 2000). The physiological relevance releasing hormone (GHRH) and somatostatin (SRIF) (Fig. 1). as well as the signal transduction mechanisms for these Within the hypothalamus, GHRH and SRIF neurons (from the phenomena, however, is still poorly understood. Recently, arcuate and periventricular nuclei, respectively) directly inner- our studies on GH autoregulation in the carp pituitary have vate the external layers of the median eminence (Leshin et al., revealed the presence of an intrapituitary feedback loop that 1994), and “180° out-of-phase” secretion of the stimulatory can regulate GH release and GH gene expression by local GHRH and inhibitory SRIF into the hypophyseal portal blood interactions between gonadotrophs and somatotrophs. This determines the pulsatile pattern of GH release (Wagner et al., feedback loop may represent a novel mechanism in fish 1998). At the pituitary level, GHRH stimulates GH release and models maintaining basal GH release and pituitary GH gene expression via the adenylate cyclase (AC)/cAMP/ MAPK responsiveness to stimulation by hypophysiotropic factors. PKA and/or PI3K/Ras/P42/44 pathways (Pombo et al., In this article, the mechanisms for feedback control of GH 2000; Wong et al., 1995). GHRH-induced GH gene expression synthesis and secretion will be summarized and the also involves CREB phosphorylation (Bertherat, 1997) and up- functional implications as well as the post-receptor regulation of Pit-1 gene expression (Chung et al., 1998). Unlike signaling mechanisms for this local feedback loop will be GHRH, SRIF inhibits GH release by AC inactivation to discussed. suppress cAMP production (Narayanan et al., 1989), inhibition Fig. 1. Feedback regulation of GH release in mammals. In the pituitary of mammals, GH release from somatotrophs is under the dual control by GHRH and SRIF. The two regulators are released by the respective neurons in the hypothalamus and delivered to the anterior pituitary via the hypophyseal portal blood system. GH release from the pituitary can exert a negative feedback on somatotrophs by three separate routes, namely (i) long-loop feedback via indirect actions of IGF-I produced in the liver, (ii) short-loop feedback by direct actions of GH acting at the hypothalamus, and (iii) ultra-short feedback by local actions of GH acting within the pituitary. GH released from the pituitary and/or produced locally in the gonad can stimulate/potentiate steroidogenesis and sex steroids in circulation can exert both positive and negative effects on somatotrophs, either directly at the pituitary level or indirectly via actions within the hypothalamus. GH can also modulate energy homeostasis in mammals, which may have an effect on the secretion of ghrelin from the stomach and leptin from white adipocytes. These hormones not only play a role in appetite control but can also act at the pituitary level to induce GH release from somatotrophs. a For short-loop feedback, GH can enter the brain by receptor-mediated transcytosis at the choroids plexus and/or by retrograde transport via the portal blood system. b For ultra-short feedback, GH can act directly on somatotrophs and/ or indirectly via local production of IGF-I at the pituitary level. c Although the stomach represents the major source of ghrelin in systemic circulation, local production of ghrelin has been reported in the hypothalamus as well as in the pituitary. 中国科技论文在线 http://www.paper.edu.cn 286 A.O.L. Wong et al. / Comparative Biochemistry and Physiology, Part A 144 (2006) 284–305 of Na+ (Kato and Sakuma, 1997) and Ca2+ channel activities 1989; Jansson et al., 1985). The influence of sex steroids on GH (Kato, 1995), and membrane hyperpolarization caused by synthesis, however, is still controversial, as stimulatory, activation of inwardly rectifying K+ current (Sims et al., 1991). inhibitory, and no effects have been reported (for review, see Although SRIF can also inhibit GHRH release from the Chowen et al., 2004). Both testosterone and estrogen, and to a hypothalamus (West et al., 1997), SRIF dose not affect GH less extent for progesterone, are known to modify the pusatile production/gene expression at the pituitary cell level (Fukata et pattern of GH release in vivo, either by changing the pulse al., 1985; Tanner et al., 1990). Based on the extensive studies in frequency (Yonezawa et al., 2005) and/or pulse amplitude the rat as well as in other animal models, it is commonly (Crowne et al., 1997; Genazzani et al., 1993). Given that accepted that GHRH and SRIF neurons in the hypothalamus gonadal steroids, e.g. testostrone, can regulate the gene represent the major target sites within the central nervous expression of GHRH in the arcuate nucleus (Zeitler et al., system for feedback control of GH synthesis and secretion 1990) and SRIF in the periventricular nucleus (Argente et al., (McMahon et al., 2001; Muller et al., 1999). 1990), these modulatory effects probably are mediated through The somatotropic and metabolic effects of GH are mediated central actions within the hypothalamus. Recently, increasing mainly by insulin-like growth factor (IGF) released from the evidence has cumulated suggesting that ghrelin from the liver (Isaksson, 2004; Muller et al., 2003). Except during the stomach (Kojima et al., 1999) and leptin from white adipose neonatal phase, IGF-I but not IGF-II is the dominant form of tissue (Zhang et al.,
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