Bridget I. Baker

Melanin-Concentrating Hormone: A General Vertebrate Neuropeptide

Publisher Summary This chapter reviews the potential roles of Melanin-Concentrating Hormone (MCH) in mammals. The MCH has a striking effect in teleost fish, causing them to become pale in color. The endocrine repertoire to comparative studies on lower vertebrates shows that identical or highly homologous hormones occur in all vertebrate classes, their physiological roles may differ. A hormone is involved with several diverse functions even within one animal, but the emphasis on a particular function can shift during the course of evolution, so that homologous hormones in fishes and mammals may serve different roles in the two classes. A hormone or neuropeptide exerting an obscure effect in mammals might elicit a response in lower vertebrates, which is the cause of its discovery. There are many examples of physiological events that are regulated by two opposing hormones, an arrangement that gives rapid and finer control than changing titers of a single hormone. The distribution of MCH perikarya and fibers is examined in few species and suggests that the organization found in bony fish may differ slightly from that in other vertebrates.

Melanin-Concentrating Hormone (MCH) Antagonizes the Effects of α-MSH and Neuropeptide E-I on Grooming and Locomotor Activities in the Rat

The intraventricular (i.c.v.) administration of the neuropeptide melanocyte stimulating hormone (alpha-MSH) is known to elicit a series of behaviors in the rat which include excessive grooming and other motor activities. In bony fish, the pigmentary effects of alpha-MSH can be antagonized by the neuropeptide melanin-concentrating hormone (MCH). We therefore examined whether MCH or its sister peptide neuro-peptide E-I (NEI), derived from the same precursor molecule, would modulate the effect of alpha-MSH on grooming and motor activity in the rat, or perhaps elicit some responses of their own. Rats were injected i.c.v. with either artificial cerebrospinal fluid, alpha-MSH, MCH, NEI, or with two peptides together, and behavioral responses were monitored over the next 65 min. The i.c.v. injection of 1 microgram MSH significantly enhanced grooming behavior. NEI at the same dose increased grooming, rearing, and locomotor activities. MCH alone had no behavioral effects but it annulled the behavioral responses induced by either alpha-MSH or NEI. alpha-MSH also antagonized the locomotor and rearing behavior induced by NEI. The physiological significance of these observations is discussed.

In the trout, CRH and AVT synergize to stimulate ACTH release

Anterior pituitaries of the rainbow trout (Oncorhynchus mykiss) were incubated with graded concentrations of arginine vasotocin (AVT) or synthetic rat corticotrophin-releasing hormone (rCRH-41), alone or in combination, and the ACTH secreted into the medium was measured by a sensitive cytochemical bioassay. The aim was to determine the relative potencies of the two secretogogues and whether, in this fish species, they act synergistically. Rat CRF-41 and AVT both produced concentration-dependent increases in ACTH release. The minimum effective concentration for both peptides was approximately 1 nM but, at higher concentrations, the efficacy of CRF-41 was greater than that of AVT. Clear evidence of synergy between the two peptides was obtained. The response of the trout thus falls in line with observations in mammals and contrasts with findings for the goldfish.

The teleost melanin-concentrating hormone—A pituitary hormone of hypothalamic origin

Abstract A simple bioassay method for the teleost melanin-concentrating hormone (MCH) is described. Using this assay and also the Anolis bioassay for melanocyte-stimulating hormone (MSH) the work compares the relative concentrations of MSH and MCH in the pituitary of various teleost species and their pattern of distribution after polyacrylamide gel electrophoresis. Neurointermediate lobes from trout were cultured and various factors [cold, cycloheximide, ethyleneglycol bis(β-aminoethyl ether) N,N′ -tetraacetic acid) (EGTA), and high K ion concentration] were examined for their effect on MSH and MCH secretion. EGTA and high K + both inhibited MSH release; cold and cycloheximide appeared to reduce MSH synthesis. Whereas these effects on MSH were predictable and consistent, the response of MCH was erratic and unpredictable. In contrast to MSH, there was no evidence for MCH synthesis in vitro . The hypothalamus of the trout contains as much MCH as the pituitary, and the concentration of MCH in the hypothalamus varies with the background colour on which the fish is kept. The evidence as a whole suggests that MCH is an hypothalamic secretion which is stored and released by the neurohypophysis.

Stimulatory Effect of Melanin-Concentrating Hormone on Luteinising Hormone Release

Alpha-melanocyte-stimulating hormone (alpha-MSH) and melanin-concentrating hormone (MCH) are two peptide neurotransmitters widely distributed in the mammalian brain, the former originating mainly from cell bodies in the arcuate nucleus and the latter from cell bodies in the zona incerta and lateral hypothalamus. Within the hypothalamus they innervate the pre-optic area, median eminence (ME) and ventromedial nucleus (VMN). Both peptides stimulate sexual behaviour and in this report we have investigated their effect on another gonadal steroid-dependent function, luteinising hormone (LH) release. alpha-MSH, MCH or a combination of the two were injected bilaterally (100 ng/side) into either the medial pre-optic area (MPOA), ME, or VMN of anaesthetised (Saffan 3 ml/kg i.p.) rats that had previously been ovariectomised and adrenalectomised (O+A) and then primed with 5 microg/rat s.c. oestradiol benzoate (OB), 48 h before peptide administration. MCH stimulated LH release when applied to the MPOA and ME; alpha-MSH was inhibitory in the ME and in this model was ineffective in the MPOA. Neither peptide was effective in the VMN. The two peptides were then injected into the MPOA of O+A rats primed with OB followed 48 h later by 0.5 mg/rat s.c. progesterone, which normally induces an LH surge. alpha-MSH, but not MCH, inhibited this induced rise in LH. Administration of anti-MCH antiserum (0.5 microg/side neat serum) also had an inhibitory effect on LH release in this model. These results show that MCH has a stimulatory effect on LH release when administered into the ME and MPOA. In the MPOA, this may be physiologically significant since blocking endogenous MCH with an anti-MCH antiserum inhibits LH release. On the other hand, alpha-MSH has an inhibitory effect on LH release in the MPOA and ME. In the teleost skin these two peptides are functionally antagonistic; it seems that a similar antagonism exists between their effects on LH release.

The effect of various stresses, corticosteroids and adrenergic agents on phagocytosis in the rainbow trout Oncorhynchus mykiss

The effect of acute and chronic stress on the phagocytic activity of putative macrophages from the rainbow trout. Oncorhynchus mykiss has been assessed, using an in vitro phagocytic index, in which the average number of engulfed yeast cells in a population of phagocytes is determined. An injection stress given under light anaesthesia, or a longer noise stress combined with confinement, both significantly reduced, within 3 h, the level of phagocytic activity of macrophages from the spleen and pronephros. Daily injection stress over six days had a lesser effect on the proportion of phagocytically active cells even though plasma cortisol levels were equally raised. Daily dexamethasone injection depressed the proportion of phagocytically active cells more than saline injection. In these in vivo experiments, it was not possible to determine whether stress and steroids depressed the phagocytic activity of individual macrophages or caused the active macrophages to migrate out of the spleen and pronephros. Administration of cortisol (200 nM) to trout macrophages in vitro failed to depress phagocytic activity within a 3h period but both α- and β-adrenergic agonists (10 μM) were usually depressive. It is proposed that the autonomic nervous system may be an early regulator of macrophage phagocytosis following stress and that corticosteroids only exert their suppressive effect on macrophage activity in the longer term.

Melanin-concentration hormone updated functional considerations

The melanin-concentrating hormone (MCH) is a vertebrate neuropeptide produced in hypothalamic perikarya whose fibers project to most regions of the brain and into the spinal cord. Its role as a neurohypophyseal color-change hormone is peculiar to teleost fish, but recent studies in mammals suggests that MCH itself, and other peptides derived from the same precursor, may participate in multiple functions in the central nervous system, modulating behavior and the perception of sensory information. Recent hybridization studies in mammals have greatly increased our understanding of the response of the MCH system to environmental factors, such as osomotic challenge, lactation, stress, and changes in corticosteroid levels. Further studies in lower vertebrates are needed to highlight the physiologically important functions that have led to the structural conservation of the MCH peptide during vertebrate evolution.

The Effects of Acute and Chronic Stresses on Vasotocin Gene Transcripts in the Brain of the Rainbow Trout (Oncorhynchus mykiss)

Secretion of adrenocorticotropic hormone (ACTH) from the fish pituitary, which occurs in times of stress, is stimulated by several hypothalamic neuropeptides, one of which is arginine vasotocin (AVT). This study investigates whether gene expression for AVT is up‐regulated during acute or chronic stress. Rainbow trout (Oncorhynchus mykiss) were subjected to one of two forms of acute stress—either 2 h confinement followed by 2 h recovery, or capture and transfer to low water for 2 min followed by 4 h recovery in their home tank before autopsy. In other experiments, these stresses were repeated daily for 5 or 6 days (chronic stress). Quantification of AVT transcript prevalence in the parvocellular and magnocellular neurones of the preoptic nucleus after in situ hybridization was used as a monitor of the AVT gene response to stress. The results showed that acute confinement, but apparently not brief low‐water stress, significantly increased AVT transcript prevalence in a group of parvocellular perikarya. When applied repeatedly, both forms of stress caused habituation, such that the AVT hybridization signal remained at control or even lower levels despite elevated pro‐opiomelanocortin transcripts in the corticotropes and raised plasma cortisol concentrations. The AVT hybridization signal in the magnocellular perikarya showed no significant response to either acute or chronic stress. The results support the idea that these parvocellular AVT neurones are involved in ACTH stimulation during acute stress, and that the system habituates to chronic stresses.

Investigations on hypothalamic control of adenohypophysial functions in teleost fishes

Abstract Various kinds of evidence for hypothalamic influences on teleost adenohypophysial functions are reviewed. Discordancies amongst the results available appear to spring from the different investigative techniques employed, and from differences among teleost species. Until the isolation of specific chemical entities, the terms “hypothalamic factor” or “hypothalamic hormone,” borrowed from mammalian literature, must be regarded simply as convenient ways of referring to hypothalamic mechanisms or influences inferred from experimental results. Within these limits, and bearing in mind the small number of species studied, we conclude that for certain species there is strong evidence for a thyrotropin-inhibitory factor and a gonadotropin-releasing factor; that there is fairly strong evidence for a corticotropin-releasing factor and a somatotropin-releasing factor; that there is evidence for both a releasing factor and an inhibiting factor for melanophore-stimulating hormone; that there appears to be a releasing factor controlling the pars intermedia PAS-positive cells of uncertain function; and that the existence of a prolactin-inhibiting factor is probable but not certain.

Cell and Molecular Cell Biology of Melanin-Concentrating Hormone

Recent advances in the study of melanin-concentrating hormone (MCH) have depended largely on molecular biological techniques. In mammals, which have attracted the most attention, novel findings concern (i) the MCH gene, which can yield several peptides by either posttranslational cleavage or alternative splicing, as well as bidirectional transcription; (ii) the identification of two G protein-coupled MCH receptors in the brain and peripheral tissues; and (iii) the evidence for subpopulations of MCH neurons in the central nervous system, characterized by their chemical phenotypes, connections, and individual physiological responses to different physiological paradigms. The involvement of central MCH in various functions, including feeding, reproduction, stress, and behavior patterns, is reviewed. The stage during evolution at which MCH may have acquired hypophysiotrophic and hormonal functions in lower vertebrates is considered in light of morphological data. Evidence that MCH also has peripheral paracrine/autocrine effects in mammals is provided.