Biomedical subjects

Kazuyoshi Tsutsui

Publications and source records attributed to Kazuyoshi Tsutsui.

At least 19 recordsLinked to original sources

PubMed2006

The general and comparative biology of gonadotropin-inhibitory hormone (GnIH).

The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin inhibit gonadotropin secretion via feedback from the gonads, but a neuropeptide inhibitor of gonadotropin secretion was, until recently, unknown in vertebrates. In 2000, we identified a novel hypothalamic dodecapeptide that inhibits gonadotropin release in cultured quail pituitaries and termed it gonadotropin-inhibitory hormone (GnIH). To elucidate the mode of action of GnIH, we then identified a novel G protein-coupled receptor for GnIH in quail. The GnIH receptor possesses seven transmembrane domains and specifically binds to GnIH. The GnIH receptor is expressed in the pituitary and several brain regions including the hypothalamus. These results indicate that GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release. GnIH may also act on the hypothalamus to inhibit GnRH release. To demonstrate the functional significance of GnIH and its potential role as a key regulatory neuropeptide in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in quail. Chronic treatment with GnIH inhibited gonadal development and maintenance by decreasing gonadotropin synthesis and release. GnIH was also found in the hypothalamus of other avian species including sparrows and chickens and also inhibited gonadotropin synthesis and release. The pineal hormone melatonin may be a key factor controlling GnIH neural function, since quail GnIH neurons express melatonin receptor and melatonin treatment stimulates the expression of GnIH mRNA and mature GnIH peptide. Thus, GnIH is capable of transducing photoperiodic information via changes in the melatonin signal, thereby influencing the reproductive axis. It is concluded that GnIH, a newly discovered hypothalamic neuropeptide, is a key factor controlling avian reproduction. The discovery of avian GnIH opens a new research field in reproductive neuroendocrinology.

Amino Acid Sequence↗

PubMed2006

Rat RFamide-related peptide-3 stimulates GH secretion, inhibits LH secretion, and has variable effects on sex behavior in the adult male rat.

A recently described avian neuropeptide, gonadotropin inhibitory hormone (GnIH), has been shown to have seasonal regulatory effects on the hypothalamic-pituitary-gonadotropin axis (HPG) in several avian species. In the bird, GnIH expression is increased during the photorefractory period and has inhibitory effects on the HPG. A recently described mammalian neuropeptide, RF-amide-related peptide-3 (RFRP-3), may be genetically related and functionally similar to this avian neuropeptide. The purposes of this study were to first see if rat RFRP-3 is expressed in the male rat brain and second to determine if ICV injections of RFRP-3 will have effects on feeding and sex behaviors, as well as hormone release from the anterior pituitary. Results confirm other studies in that immunoreactive cell bodies and fibers are observable in areas of the male rat brain known to control the HPG and feeding and sex behaviors. RFRP-3 fibers are also observed in close proximity to GnRH immunoreactive cell bodies. Behavioral tests indicate that high but not low ICV RFRP-3 (500 vs. 100 ng, respectively) significantly (p<0.05) suppressed all facets of male sex behavior while not having any observable effects on their ability to ambulate. Sex behavior was later exhibited when those same male rats received the ICV vehicle. While suppressing sex behavior, ICV RFRP-3 significantly (p<0.05) increased food intake compared to controls. ICV RFRP-3 also significantly reduced plasma levels of luteinizing hormone but increased growth hormone regardless of the time of day; however, at no time did RFRP-3 alter plasma levels of FSH, thyroid hormone, or cortisol. These results indicate that although RFRP-3 has similar effects on LH as observed with GnIH in avian species, in the rat RFRP-3 has additional roles in regulating feeding and growth.

Animals↗

PubMed2006

Molecular cloning and functional characterization of a prolactin-releasing peptide homolog from Xenopus laevis.

Amino acid sequences for identified prolactin (PRL)-releasing peptides (PrRPs) were conserved in mammals (>90%) or teleost fishes (100%), but there were considerable differences between these classes in the sequence (<65%) as well as in the role of PrRP. In species other than fishes and mammals, we have identified frog PrRP. The cDNA encoding Xenopus laevis prepro-PrRP, which can generate putative PrRPs, was cloned and sequenced. Sequences for the coding region showed higher identity with teleost PrRPs than mammalian homologues, but suggested the occurrence of putative PrRPs of 20 and 31 residues as in mammals. The amino acid sequence of PrRP20 was only one residue different from teleost PrRP20, but shared 70% identity with mammalian PrRP20s. In primary cultures of bullfrog (Rana catesbeiana) pituitary cells, Xenopus PrRPs increased prolactin concentrations in culture medium to 130-160% of the control, but PrRPs was much less potent than thyrotropin-releasing hormone (TRH) causing a three- to four-fold increase in prolactin concentrations. PrRP mRNA levels in the developing Xenopus brain peak in early prometamorphosis, different from prolactin levels. PrRP may not be a major prolactin-releasing factor (PRF), at least in adult frogs, as in mammals.

Amino Acid Sequence↗

PubMed2006

Neurosteroid biosynthesis in the quail brain: a review.

The brain traditionally has been considered to be a target site of peripheral steroid hormones. In contrast to this classical concept, new findings over the past decade have shown that the brain itself also has the capability of forming steroids de novo, the so-called "neurosteroids". De novo neurosteroidogenesis in the brain from cholesterol is a conserved property of vertebrates. Our studies using the quail, as an excellent animal model, have demonstrated that the avian brain possesses cytochrome P450 side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD), cytochrome P450 17alpha-hydroxylase/c17,20-lyase (P450(17alpha,lyase)), 17beta-HSD, etc., and produces pregnenolone, progesterone, 3beta, 5beta-tetrahydroprogesterone, androstenedione, testosterone and estradiol from cholesterol. However, the biosynthetic pathway of neurosteroids in the avian brain from cholesterol may be still incomplete, because we recently found that the quail brain actively produces 7alpha-hydroxypregnenolone, a previously undescribed avian neurosteroid. This paper summarize the advances made in our understanding of biosynthesis of neurosteroids in the avian brain.

Androgens↗

PubMed2006

Structures and diverse functions of frog growth hormone-releasing peptide (fGRP) and its related peptides (fGRP-RPs): a review.

A new Arg-Phe-NH(2) (RFamide) peptide has been discovered in the amphibian hypothalamus. The cell bodies and terminals containing this peptide were localized in the suprachiasmatic nucleus and median eminence, respectively. This peptide was further revealed to have a considerable growth hormone (GH)-releasing activity in vitro and in vivo and hence designated as frog GH-releasing peptide (fGRP). Molecular cloning of cDNA encoding the fGRP precursor polypeptide revealed that it encodes fGRP and its putative gene-related peptides (fGRP-RP-1, -RP-2, and -RP-3). Subsequently, we identified these putative fGRP-RPs as mature peptides and analyzed their hypophysiotropic activities. Only fGRP-RP-2 stimulated the release of GH and prolactin (PRL) in vitro and in vivo. Thus, in addition to fGRP, fGRP-RP-2 acts as a hypothalamic factor on the frog pituitary to stimulate the release of GH and PRL.

Amino Acid Motifs↗

PubMed2006

Mode of action and functional significance of avian gonadotropin-inhibitory hormone (GnIH): a review.

Neuropeptide control of gonadotropin secretion at the level of the anterior pituitary gland is primarily through the stimulatory action of the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH). However, a hypothalamic neuropeptide acting at the level of the pituitary to negatively regulate gonadotropin secretion has, until recently, remained unknown in any vertebrate. In 2000, we discovered a novel hypothalamic neuropeptide inhibiting gonadotropin release at the level of the pituitary in quail and termed it gonadotropin-inhibitory hormone (GnIH). A gonadotropin-inhibitory system is an intriguing concept and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To elucidate the mode of action of GnIH, we further identified the receptor for GnIH and characterized its expression and binding activity in quail. The identified GnIH receptor possessed seven transmembrane domains and specifically bound to GnIH in a concentration-dependent manner. The expression of GnIH receptor was found in the pituitary and several brain regions including the hypothalamus. These results suggest that GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release. GnIH may also act on the hypothalamus to inhibit GnRH release. To understand the functional significance of GnIH in avian reproduction, we also investigated the mechanism that regulates GnIH expression. Interestingly, melatonin induced dose-dependently GnIH expression and melatonin receptor (Mel(1c)) was expressed in GnIH neurons. Thus melatonin appears to act directly on GnIH neurons via its receptor to induce GnIH expression. Based on these studies, GnIH is likely an important neuropeptide for the regulation of avian reproduction.

Amino Acid Sequence↗

PubMed2006

Interactions of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH) in birds and mammals.

Gonadotropin-releasing hormone (GnRH) regulates secretion of both of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone. Thus, it is a key hormone for vertebrate reproduction. GnRH was considered to be unusual among hypothalamic neuropeptides in that it appeared to have no direct antagonist, although some neurochemicals and peripheral hormones (opiates, GABA, gonadal steroids, inhibin) can modulate gonadotropin release to a degree. Five years ago, a vertebrate hypothalamic neuropeptide that inhibited pituitary gonadotropin release in a dose-dependent manner was discovered in quail by Tsutsui et al. (2000. Biochem Biophys Res Commun 275:661-667). We now know that this inhibitory peptide, named gonadotropin-inhibitory hormone, or GnIH, is a regulator of gonadotropin release in vitro and in vivo. Its discovery has opened the door to an entirely new line of research within the realm of reproductive biology. In our collaborative studies, we have begun to elucidate the manner in which GnIH interacts with GnRH to time release of gonadotropins and thus time reproductive activity in birds and mammals. This paper reviews the distribution of GnIH in songbirds relative to GnRHs, and our findings on its modes of action in vitro and in vivo, based on laboratory and field studies. These data are simultaneously compared with our findings in mammals, highlighting how the use of different model species within different vertebrate classes can be a useful approach to identify the conserved actions of this novel neuropeptide, along with its potential importance to vertebrate reproduction.

Animals↗

PubMed2006

Control of luteinizing hormone and testosterone secretion in a flexibly breeding male passerine, the Rufous-winged Sparrow, Aimophila carpalis.

Rufous-winged Sparrows, Aimophila carpalis, reside in the Sonoran desert and although testicular development is initiated in the spring under the influence of increasing day length, breeding occurs opportunistically in summer in association with heavy rainfall or "monsoon". The aim of this study in free-living male Rufous-winged Sparrows was to establish the relationship between concentrations of plasma luteinizing hormone (LH) and testosterone (T), and breeding associated with heavy rainfall, and to investigate whether breeding is mediated by changes in pituitary gland sensitivity to gonadotropin releasing hormone-I (GnRH) and the recently discovered avian gonadotropin-inhibitory hormone (GnIH). Concentrations of plasma LH and T were relatively low until mid-summer, but increased rapidly and transiently immediately prior to the monsoon which occurred after the summer solstice, when day lengths were decreasing. At this time the birds came into full breeding condition. An injection of chicken GnRH (10 ng) increased plasma LH within 2 min when given before or during the monsoon. An injection of GnIH (1 microg) did not affect plasma LH within 2 min during the monsoon and did not decrease GnRH-elicited LH secretion before or during the monsoon. No experimental treatment affected plasma T concentrations. The data suggest in male Rufous-winged Sparrows that the seasonal increase in plasma LH associated with summer monsoon results from increased stimulation of the pituitary gland by GnRH, rather than from a change in the responsiveness of the gland to GnRH, and that GnIH does not play an acute role in this mechanism. However, a possible chronic role for GnIH in the seasonal control of LH synthesis and secretion through an inhibitory effect on the hypothalamic GnRH system remains to be investigated.

Animals↗

PubMed2006

Hypothalamic LPXRF-amide peptides in vertebrates: identification, localization and hypophysiotropic activity.

Probing undiscovered neuropeptides that play important roles in the regulation of pituitary function in vertebrates is essential for the progress of neuroendocrinology. Recently, we identified a novel hypothalamic neuropeptide with a C-terminal LPLRF-amide sequence in the quail brain. This avian neuropeptide was shown to be located in the hypothalamo-hypophysial system and to decrease gonadotropin release from cultured anterior pituitary. We, therefore, designated this novel neuropeptide as gonadotropin-inhibitory hormone (GnIH). We further identified novel hypothalamic neuropeptides closely related to GnIH in the brains of other vertebrates, such as mammals, amphibians, and fish. The identified neuropeptides possessed a LPXRF-amide (X = L or Q) motif at their C-termini. These LPXRF-amide peptides also were localized in the hypothalamus and other brainstem areas and regulated pituitary hormone release. Subsequently, cDNAs that encode LPXRF-amide peptides were characterized in vertebrate brains. In this review, we summarize the identification, localization, and hypophysiotropic activity of these newly identified hypothalamic LPXRF-amide peptides in vertebrates.

Amino Acid Sequence↗

PubMed2006

Rapid inhibition of female sexual behavior by gonadotropin-inhibitory hormone (GnIH).

Gonadotropin-releasing hormone (GnRH) is largely responsible for the initiation of sexual behaviors; one form of GnRH activates a physiological cascade causing gonadal growth and gonadal steroid feedback to the brain, and another form is thought to act as a neurotransmitter to enhance sexual receptivity. In contrast to GnRH, gonadotropin-inhibitory hormone (GnIH) inhibits gonadotropin release. The distribution of GnIH in the avian brain suggests that it has not only hypophysiotropic actions but also unknown behavioral actions. GnIH fibers are present in the median eminence (ME) and are in apparent contact with chicken GnRH (cGnRH)-I and -II neurons and fibers. In birds, cGnRH-I regulates pituitary gonadotropin release, whereas cGnRH-II enhances copulation solicitation in estradiol-primed females exposed to male song. In the present study, we determined the effects of GnIH administered centrally to female white-crowned sparrows. A physiological dose of GnIH reduced circulating LH and inhibited copulation solicitation, without affecting locomotor activity. Using rhodaminated GnIH, putative GnIH binding sites were seen in the ME close to GnRH-I fiber terminals and in the midbrain on or close to GnRH-II neurons. These data demonstrate direct effects of GnIH upon reproductive physiology and behavior, possibly via separate actions on two forms of GnRH.

Animals↗

PubMed2006

Identification and characterization of a gonadotropin-inhibitory system in the brains of mammals.

Successful reproduction requires maintenance of the reproductive axis within fine operating limits through negative feedback actions of sex steroids. Despite the importance of this homeostatic process, our understanding of the neural loci, pathways, and neurochemicals responsible remain incomplete. Here, we reveal a neuropeptidergic pathway that directly links gonadal steroid actions to regulation of the reproductive system. An RFamide (Arg-Phe-NH2) peptide that inhibits gonadotropin release from quail pituitary was recently identified and named gonadotropin-inhibitory hormone (GnIH). Birds are known to have specialized adaptations associated with gonadotropin-releasing hormone (GnRH) regulation to optimize reproduction (e.g., encephalic photoreceptors), and the existence of a hypothalamic peptide inhibiting gonadotropins may or may not be another such specialization. To determine whether GnIH serves as a signaling pathway for sex steroid regulation of the reproductive axis, we used immunohistochemistry and in situ hybridization to characterize the distribution and functional role of this peptide in hamsters, rats, and mice. GnIH-immunoreactive (GnIH-ir) cell bodies are clustered in the mediobasal hypothalamus with pronounced projections and terminals throughout the CNS. In vivo GnIH administration rapidly inhibits luteinizing hormone secretion. Additionally, GnIH-ir neurons form close appositions with GnRH cells, suggesting a direct means of GnRH modulation. Finally, GnIH-ir cells express estrogen receptor-alpha and exhibit robust immediate early gene expression after gonadal hormone stimulation. Taken together, the distribution of GnIH efferents to neural sites regulating reproductive behavior and neuroendocrine secretions, expression of steroid receptors in GnIH-ir nuclei, and GnIH inhibition of luteinizing hormone secretion indicate the discovery of a system regulating the mammalian reproductive axis.

Amino Acid Sequence↗

PubMed2006

Biosynthesis, mode of action and functional significance of neurosteroids in the developing Purkinje cell.

New findings over the past decade have shown that the brain has the capability of forming steroids de novo from cholesterol, the so-called "neurosteroids". To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently, we have demonstrated that the Purkinje cell, a cerebellar neuron, is a major site for neurosteroid formation in a variety of vertebrates. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. Since this discovery, organizing actions of neurosteroids are becoming clear by the studies on mammals using the Purkinje cell as an excellent cellular model. In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. The Purkinje cell may also produces estradiol in the neonate. Interestingly, both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such organizing actions may contribute to the formation of cerebellar neuronal circuit during neonatal life. This paper summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of neurosteroids in the developing Purkinje cell.

Animals↗

PubMed2006

Biosynthesis and organizing action of neurosteroids in the developing Purkinje cell.

Probing undiscovered neurosubstances that play important roles in the regulation of cerebellar function is essential for the progress of our understanding of the cerebellum. New findings over the past decade have established that the cerebellum as well as other brain regions synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroidogenic glands. Such steroids synthesized de novo in the brain are called neurosteroids. Recently the Purkinje cell, a cerebellar neuron, has been identified as a major site for neurosteroid formation in the brain. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. In mammals, the Purkinje cell actively synthesizes progesterone de novo from cholesterol during neonatal life, when cerebellar cortical formation occurs. 3alpha,5alpha-Tetrahydroprogesterone (allopregnanolone) is metabolized from progesterone in the neonatal cerebellum. Estrogen formation in the Purkinje cell may also occur in the neonate. Subsequently, recent studies on mammals using the Purkinje cell have demonstrated organizing actions of neurosteroids. Both progesterone and estradiol promote dendritic growth, spinogenesis and synaptogenesis via each cognate nuclear receptor in Purkinje neurons. Allopregnanolone is also involved in Purkinje and granule cell survival. Thus the Purkinje cell serves as an excellent cellular model for understanding the formation of cerebellar neuronal circuit in relation to organizing actions of neurosteroids.

Animals↗

PubMed2006

Evolutionary origin and divergence of PQRFamide peptides and LPXRFamide peptides in the RFamide peptide family. Insights from novel lamprey RFamide peptides.

Among the RFamide peptide groups, PQRFamide peptides, such as neuropeptide FF (NPFF) and neuropeptide AF (NPAF), share a common C-terminal Pro-Gln-Arg-Phe-NH(2) motif. LPXRFamide (X = L or Q) peptides, such as gonadotropin-inhibitory hormone (GnIH), frog growth hormone-releasing peptide (fGRP), goldfish LPXRFamide peptide and mammalian RFamide-related peptides (RFRPs), also share a C-terminal Leu-Pro-Leu/Gln-Arg-Phe-NH(2) motif. Such a similar C-terminal structure suggests that these two groups may have diverged from a common ancestral gene. In this study, we sought to clarify the evolutionary origin and divergence of these two groups, by identifying novel RFamide peptides from the brain of sea lamprey, one of only two extant groups of the oldest lineage of vertebrates, Agnatha. A novel lamprey RFamide peptide was identified by immunoaffinity purification using the antiserum against LPXRFamide peptide. The lamprey RFamide peptide did not contain a C-terminal LPXRFamide motif, but had the sequence SWGAPAEKFWMRAMPQRFamide (lamprey PQRFa). A cDNA of the precursor encoded one lamprey PQRFa and two related peptides. These related peptides, which also had the C-terminal PQRFamide motif, were further identified as mature endogenous ligands. Phylogenetic analysis revealed that lamprey PQRFamide peptide precursor belongs to the PQRFamide peptide group. In situ hybridization demonstrated that lamprey PQRFamide peptide mRNA is expressed in the regions predicted to be involved in neuroendocrine and behavioral functions. This is the first demonstration of the presence of RFamide peptides in the agnathan brain. Lamprey PQRFamide peptides are considered to have retained the most ancestral features of PQRFamide peptides.

Amino Acid Sequence↗

PubMed2006

Novel fish hypothalamic neuropeptides stimulate the release of gonadotrophins and growth hormone from the pituitary of sockeye salmon.

We recently identified a cDNA encoding three novel fish hypothalamic neuropeptides, having LPXRF-NH(2) from the goldfish brain. In this study, to clarify the physiological functions of these three LPXRFamide peptides (gfLPXRFa-1, -2, and -3), we analysed the localisation and hypophysiotrophic activity of these peptides using sockeye salmon, Oncorhynchus nerka, in which immunoassay systems for several anterior pituitary hormones have been developed. gfLPXRFa-immunoreactive cell bodies were detected in the nucleus posterioris periventricularis of the hypothalamus and immunoreactive fibres were distributed in various brain regions and the pituitary. We also detected gfLPXRFa-immunoreactivity in the pituitary by competitive enzyme-linked immunosorbent assay combined with reversed-phase HPLC. These three gfLPXRFamide peptides stimulated the release of FSH, LH and GH, but did not affect the release of prolactin (PRL) and somatolactin (SL) from cultured pituitary cells. These results suggest that novel fish hypothalamic LPXR-Famide peptides exist in the brain and pituitary of sockeye salmon and stimulate the release of gonadotrophins and GH from the pituitary.

Animals↗

PubMed2006

Neural interaction of gonadotropin-regulating hormone immunoreactive neurons and the suprachiasmatic nucleus with the paraventricular organ in the Japanese grass lizard (Takydromus tachydromoides).

Our previous study demonstrated that the paraventricular organ (PVO) in the hypothalamus of the Japanese grass lizard (Takydromus tachydromoides) showed immunoreactivity against the light signal-transducing G-protein, transducin. This finding suggested that the PVO was a candidate for the deep-brain photoreceptor in this species. To understand functions of the PVO, we investigated distributions of transducin, serotonin, gonadotropin-releasing hormone (GnRH), and gonadotropin-inhibitory hormone (GnIH) in the lizard's brain. We immunohistochemically confirmed co-localization of transducin and serotonin in PVO neurons that showed structural characteristics of cerebrospinal fluid (CSF)-contacting neurons. GnRH-immunoreactive (ir) cells were localized in the posterior commissure and lateral hypothalamic area. Some of the serotonin-ir fibers extending from the PVO to the lateral hypothalamic area contacted the GnRH-ir cell bodies. GnIH-ir cells were localized in the nucleus accumbens, paraventricular nucleus, and upper medulla, and GnIH-ir fibers from the paraventricular nucleus contacted the lateral processes of serotonin-ir neurons in the PVO. In addition, we found that serotonin-ir fibers from the PVO extended to the suprachiasmatic nucleus (SCN), and the retrograde transport method confirmed the PVO projections to the SCN. These findings suggest that the PVO, by means of innervation mediated by serotonin, plays an important role in the regulation of pituitary function and the biological clock in the Japanese grass lizard.

Animals↗

PubMed2005

Gonadotropin-inhibitory hormone inhibits gonadal development and maintenance by decreasing gonadotropin synthesis and release in male quail.

Until recently, any neuropeptide that directly inhibits gonadotropin secretion had not been identified. We recently identified a novel hypothalamic dodecapeptide that directly inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). The action of GnIH on the inhibition of gonadotropin release is mediated by a novel G protein-coupled receptor in the quail pituitary. This new gonadotropin inhibitory system is considered to be a widespread property of birds and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To understand the physiological role(s) of GnIH in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in male quail. Continuous administration of GnIH to mature birds via osmotic pumps for 2 wk decreased the expressions of gonadotropin common alpha and LHbeta subunit mRNAs in a dose-dependent manner. Plasma LH and testosterone concentrations were also decreased dose dependently. Furthermore, administration of GnIH to mature birds induced testicular apoptosis and decreased spermatogenic activity in the testis. In immature birds, daily administration of GnIH for 2 wk suppressed normal testicular growth and rise in plasma testosterone concentrations. An inhibition of juvenile molt also occurred after GnIH administration. These results indicate that GnIH inhibits gonadal development and maintenance through the decrease in gonadotropin synthesis and release. GnIH may explain the phenomenon of photoperiod-induced gonadal regression before an observable decline in hypothalamic GnRH in quail. To our knowledge, GnIH is the first identified hypothalamic neuropeptide inhibiting reproductive function in any vertebrate class.

Animals↗

PubMed2005

Gonadotropin-inhibiting hormone stimulates feeding behavior in chicks.

Neuropeptides containing a C-terminal Arg-Phe-NH2 motif (RFamide peptides) are suggested to be involved in the control of feeding behavior in both invertebrates and vertebrates. Gonadotropin-inhibitory hormone (GnIH) is the first identified avian RFamide peptide that inhibits gonadotropin release from the pituitary. The GnIH precursor encodes one GnIH and its related peptides (GnIH-RP-1 and -RP-2) that shared the same C-terminal motif, Leu-Pro-Xaa-Arg-Phe-NH2 (Xaa = Leu or Gln) (LPXRFamide). GnIH neurons are localized in the paraventricular nucleus, with their fibers visible in multiple brain locations including the median eminence and brainstem. In this study, we therefore investigated the action of GnIH and its related peptides on feeding behavior. Intracerebroventricular (ICV) injection of GnIH, GnIH-RP-1 and GnIH-RP-2 significantly stimulated food intake in chicks. The chicken pentapeptide LPLRFamide, a degraded C-terminus of GnIH and GnIH-RP-1, did not stimulate feeding thereby demonstrating the importance of the N-terminus of GnIH and its related peptides for the orexigenic effect. Anti-GnIH antiserum suppressed appetite induced by fasting, but did not modify feeding under ad libitum conditions. The present study suggests that GnIH and its related peptides act as endogenous orexigenic factors in the brain of chicks.

Amino Acid Sequence↗