José Miguel Cerdá-Reverter

The central melanocortin system regulates food intake in goldfish

Posttranscriptional processing of proopiomelanocortin (POMC) yields melanocortin peptides, which are involved in the regulation of energy balance in mammals. The sequence preservation of the main brain melanocortin, alpha-melanocyte-stimulating hormone (alpha-MSH), suggests a conserved function throughout vertebrate evolution. We studied the involvement of the central melanocortin system in the control of food intake in the goldfish. In situ hybridization studies done following molecular cloning of POMC mRNA demonstrated positive POMC mRNA cell bodies exclusively expressed within the mediobasal hypothalamus, in the anterior, posterior and inferior part of the lateral tuberal nucleus and the medial region of the lateral recess nucleus. POMC expression is localized in brain areas appropriate for involvement in food intake and neuroendocrine regulation. Progressive fasting did not affect POMC mRNA expression levels. Intracerebroventricular administration of [Nle(4), D-Phe(7)]-alpha-MSH (NDP-alpha-MSH), a universal melanocortin agonist, within nanomolar range, dose-dependently inhibited food intake 2 h after treatment. The results show for the first time a functional melanocortin system in fishes that participates in central regulation of food intake. The conserved central expression pattern of POMC mRNA and role of MSH peptides in physiological regulation of food intake suggests that melanocortin functions were gained early in vertebrate evolution.

Molecular cloning, characterization and brain mapping of the melanocortin 5 receptor in the goldfish

The melanocortin 5 receptor (MC5R) is activated by melanocyte‐stimulating hormones (MSHs) and has a widespread tissue distribution, while its detailed central expression pattern and brain functions are fairly unknown. We report cloning, pharmacological characterization, tissue distribution and detailed brain mapping of melanocortin 5 receptor in goldfish (gMC5R). The goldfish orthologue protein is 69% identical to human MC5R and is conserved in important functional domains. The gMC5R showed similar potency to α‐, β‐ and γ‐MSH peptides in radioligand binding as the mammalian orthologues, while MTII and HS024 were both agonists at this receptor. The gMC5R‐mRNA was found in the peripheral tissues including kidney, spleen, skin and retina, with low expression levels in the intestine, fat, muscle, gill, pituitary and ovary. In situ hybridization studies demonstrated that gMC5R transcripts are widely distributed in the goldfish brain. The gMC5R expression was found in ventral telencephalon, pre‐optic area, dorsal and ventral thalamus, infundibular hypothalamus, posterior tuberculum, tectum and tegmentum mesencephali, reticular formation, vagal and facial lobes and spinal cord. The cloning and characterization of this receptor provides an important tool to elucidate its participation in neuroendocrine and behavioural control.

Regulation of the Hypothalamic Melanin-Concentrating Hormone Neurons by Sex Steroids in the Goldfish: Possible Role in the Modulation of Luteinizing Hormone Secretion

In teleost fish, melanin-concentrating hormone (MCH) is a cyclic heptadecapeptide released from the pituitary during white background adaptation. In the periphery MCH concentrates melanin granules in melanophores thus lightening the body color of fish. Evidence from mammalian studies has demonstrated the involvement of MCH in the control of energy balance and the reproductive axis. Information about the hormonal regulation of MCH neurons in non-mammalian systems is scarce and nothing is known about its role in the regulation of the reproductive axis. We here report the molecular characterization of two MCH precursors in the goldfish. Both precursors are peripherally expressed and the expression in the central nervous system is restricted to the mediobasal hypothalamus. Hypothalamic MCH-mRNA production is upregulated during white background adaptation. Both testosterone and estradiol stimulate MCH mRNA expression in the hypothalamus in a sex-dependent manner, with females showing the greatest responsiveness. In addition, in vitroexperiments demonstrated that graded doses of salmon MCH stimulate LH, but not GH, secretion from dispersed pituitary cells. Results suggest that hypothalamic MCH may participate in the steroid positive feedback loop on pituitary LH secretion.

Brain mapping of three somatostatin encoding genes in the goldfish

In the present study the brain distribution of three somatostatin (SRIF)‐encoding genes, PSS‐I, PSS‐II, and PSS‐III, was analyzed by in situ hybridization (ISH) in the goldfish. The PSS‐I mRNA showed the widest distribution throughout the brain, whereas PSS‐II transcripts were restricted to some hypothalamic nuclei. On the other hand, PSS‐III presents an intermediate distribution pattern. All SRIF encoding genes are expressed in hypophysiotropic nuclei supporting the idea that, in addition to SRIF‐14, [Pro2] SRIF‐14, and gSRIF‐28 have pituitary‐controlling functions. Moreover, each of the genes is expressed in nuclei directly associated with feeding behavior, suggesting a role for SRIF peptides in the central control of food intake and energy balance. Alternatively, they might have a role in processing sensory information related with feeding behavior, since PSS genes are expressed in the main gustatory, olfactory, and visual centers, which project to the hypothalamic feeding center in teleost fish. J. Comp. Neurol. 474:43–57, 2004.

Chapter 1 Neuroendocrine Systems of the Fish Brain

Publisher Summary This chapter discusses the neuroendocrine territories in fish. It describes the anatomy of the main neuroendocrine territories of the teleost brains. Teleost fish lack a canonical median eminence, and the hypothalamic neurons terminate very close to the adenohypophysial cells or make synaptoid contact upon them. This anatomical characteristic allows the study of the hypothalamo–hypophysial system by retrograde tracing experiments. Tract‐tracing techniques have corroborated early studies showing the preoptic area and tuberal hypothalamus as loci for the neuronal cell bodies whose axons reach the neuro‐ and adenohypophysis along well‐defined fiber tracts. The chapter also discusses several neuronal systems that produce hypothalamic releasing or inhibitory peptides and neurotransmitters, and innervate the pituitary. The hypothalamus–pituitary complex in teleost species shows a particular specialization in which the median eminence is greatly reduced or absent. As a consequence, the hypothalamic control of the pituitary is exerted by an important pituitary innervation that penetrates to the adenohypophysis as interdigitation of neuronal tissue. This neuronal circuitry integrates incoming information from both external and internal environments by expressing the appropriate set of hormonal receptors and through interneuronal communication.