Differential action of secreto-inhibitors on proopiomelanocortin biosynthesis in the intermediate pituitary of Xenopus laevis.

Dotman, C.H.; Cruijsen, Peter M. J. M.; Jenks, Bruce G.; Roubos, Eric W.

doi:10.1210/endo.137.11.8895316

Cited by 22 publications

(9 citation statements)

References 14 publications

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“…These findings indicate that in amphibians, GABA can also regulate melanotrope function through the inhibition of POMC gene expression. In support of this notion, GABA receptor agonists have been shown to suppress POMC biosynthesis in cultured neurointermediate lobes from the toad X. laevis [36]. A similar situation occurs in the rat intermediate lobe, where GABA exerts a direct inhibitory effect on POMC gene expression in melanotrope cells [37].…”

Section: Discussionmentioning

confidence: 97%

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

et al. 2001

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The melanotrope population of the frog intermediate lobe consists of two subtypes of cells, referred to as high-(HD) and low-density (LD) melanotrope cells, which differ markedly in their basal morphofunctional features as well as their in vitro response to hypothalamic factors, such as the stimulator thyrotropin-releasing hormone (TRH) and the inhibitor dopamine. In this study, we have investigated whether other major hypothalamic regulators of the release of α-melanocyte-stimulating hormone (α-MSH), such as γ-aminobutyric acid (GABA) and neuropeptide Y (NPY), also differentially regulate frog melanotrope subpopulations. Our results show that in LD cells, both factors markedly inhibited proopiomelanocortin (POMC) mRNA accumulation and α-MSH secretion. In contrast, the secretory and biosynthetic activity of HD cells was not modified by GABA. NPY inhibited POMC transcript accumulation and tended to reduce α-MSH secretion in HD cells, yet these effects were less pronounced than those evoked in LD cells. In addition, GABA and NPY inhibited the KCl-induced rise in cytosolic free calcium levels in both subpopulations. Taken together, these results further indicate that frog melanotrope subpopulations are differentially regulated by the hypothalamus and strongly suggest that the intensity of such regulation is directly related to the activity of the cell subset. Thus, the LD subpopulation represents a highly responsive cell subset which is regulated by multiple neuroendocrine factors (TRH, dopamine, GABA and NPY), whereas the hormone storage HD subpopulation shows a moderate response to single stimulatory (TRH) and inhibitory (NPY) inputs.

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Section: Discussionmentioning

confidence: 97%

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

et al. 2001

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“…As to the mechanism(s) that are responsible for the expression of c-Fos (and FRAs) in the Xenopus melano trope, various neural messengers, known either to stimu late (CRH, TRH) or to inhibit (DA, NPY) POMC biosyn thesis in the Xenopus melanotrope [17,18] are good can didates. Except for TRH, they all regulate cAMP produc tion, which is relevant as in mammals overexpression of c-Fos results in activation of POMC gene transcription via a cyclic AMP/protein kinase-A-dependent mecha nism.…”

Section: Control O F Fos Expressionmentioning

confidence: 99%

“…Except for TRH, they all regulate cAMP produc tion, which is relevant as in mammals overexpression of c-Fos results in activation of POMC gene transcription via a cyclic AMP/protein kinase-A-dependent mecha nism. Among these messengers, CRH is a likely c-Fos stimulator as it enhances c-fos gene expression in mam mals [43] and increases FosB expression in the AtT-20 corticotrope cell line [44], As to the inhibition of c-Fos expression, it is interesting to note that NPY has a long term inhibitory action on the biosynthesis of melanotrope POMC [ 17], As NPY is a physiological regulator of mela notrope cell activity during adaptation on a white back ground, this long-term inhibition exerted by NPY might well be related to the observed long-term decrease in Fos-LI expression on this background.…”

Section: Control O F Fos Expressionmentioning

confidence: 99%

Physiologically Induced Fos Expression in the Hypothalamo-Hypophyseal System of <i>Xenopus laevis</i>

Ubink¹,

Jenks²,

Roubos³

1997

Neuroendocrinology

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The amphibian Xenopus laevis adjusts the color of its skin to the degree of background illumination. The neuroendocrine mechanism responsible for this adaptation behavior involves various brain centers that control the synthesis and release of α-melanophore-stimulating hormone (α-MSH) by the pituitary melanotrope cells. The aim of the present study was to investigate the possible use of Fos as a tool to determine the activity of known and novel components of this mechanism. For this purpose, a quantitative Fos-immunocytochemical method (ABC) was successfully introduced for Xenopus, and the degree of specificity of background illumination as a regulator of Fos expression was tested by comparing this stimulus with two other stimuli, viz. a strong stressor (saline immersion) and a mild stressor (‘handling’). Without stimulation basal Fos-like immunoreactivity (Fos-LI) was found in the telencephalon, the lateral pallium, the anterior, central and lateral thalamic nuclei, the suprachiasmatic nucleus, the ventral hypothalamic nucleus and the torus semicircularis. Handling had no effect on this basal pattern of Fos-LI. Saline immersion induced Fos-LI only in the magnocellular preoptic nucleus, the corticotrope cells and, less strongly, in the melanotrope cells. Melanotropes, and no other cells, expressed Fos-LI very strongly when Xenopus was transferred from a white to a black background. This Fos-LI expression continued to increase up to 7 days of stimulation. When such toads were returned to a white background it took the same time before Fos-LI expression significantly dropped. It is concluded that the ABC-Fos immunocytochemistry can be successfully applied to assess the occurrence and degree of expression of Fos-LI in the Xenopus brain and pituitary gland. The prolonged expression of Fos-LI in the pars intermedia under black background stimulation and the presence of an AP-1 binding site on the Xenopus proopiomelanocortin gene suggest an important role for c-Fos and/or Fos-related antigens in the control of the biosynthesis and secretion of α-MSH by the Xenopus melanotrope cell.

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“…The secretion-inhibitory factors dopamine, yaminobutyric acid (GABA) and neuropeptide Y (NPY) [9][10][11][12] have a differential effect on POMC biosynthesis in the Xenopus pituitary pars intermedia. A long-term role in inhibitory control of POMC biosynthesis was shown for dopamine and NPY, whereas GABA has mainly short term effects [ 13], The present study is concerned with the possible stimulatory control of POMC biosynthesis by hypothalamic messengers. In the magnocellular nucleus of the hypothalamus, neurons containing corticotropinreleasing hormone (CRH) and thyrotropin-releasing hor mone (TRH) are present that project to the pituitary neu ral lobe [8].…”

Section: Introductionmentioning

confidence: 94%

Sauvagine and TRH Differentially Stimulate Proopiomelanocortin Biosynthesis in the <i>Xenopus laevis </i>Intermediate Pituitary

Dotman

Maia²,

Jenks³

et al. 1997

Neuroendocrinology

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In the amphibian Xenopus laevis, adaptation of the skin color to background light intensity is regulated by α-melanophore-stimulating hormone (α-MSH), a proopiomelanocortin (POMC)-derived peptide. In animals adapted to a white background, the level of POMC biosynthesis in the intermediate pituitary is much lower than in animals adapted to a black background. Release of α-MSH from neurointermediate lobes of white-adapted animals is stimulated in vitro by the regulatory peptides sauvagine and thyrotropin-releasing hormone (TRH), which are produced in the magnocellular nucleus of the hypothalamus. To study the role of sauvagine, cAMP, TRH and phorbol 12-myristate 13-acetate (PMA) in the regulation of POMC biosynthesis, the degree of incorporation of radioactive amino acids into the POMC protein was determined after treatment of the neurointermediate lobes with these secretagogues. When lobes of white-adapted animals are incubated in vitro, biosynthetic activity spontaneously increases because hypothalamic inhibitory control is removed by dissection. In addition to this control situation, the effects of secretagogues were tested on lobes with an inhibited level of biosynthesis, which is achieved by addition of neuropeptide Y (NPY) to the incubation medium. After 24 h of treatment, TRH stimulated POMC biosynthesis in NPY-inhibited lobes of white-adapted animals from 40.2 to 95.3% of control level. This stimulation could not be reduced by adding PMA, which indicates that protein kinase C is not involved in the stimulation of POMC biosynthesis by TRH. Sauvagine partially restored POMC biosynthesis from 27.2 to 62.5% of control level, whereas 8-Br-cAMP completely counteracted NPY inhibition from 27.8 to 97.5% of control level. After 3 days of treatment, stimulation by sauvagine and 8-Br-cAMP was maintained (sauvagine increased POMC biosynthesis in NPY-inhibited lobes from 7.4 to 36.2% of control level and 8-Br-cAMP stimulated from 6.5 to 82.5% of control level). TRH had no effect on POMC biosynthesis after 3 days of treatment, although its receptor was still functional as was shown in superfusion experiments where TRH stimulated α-MSH secretion. The observations indicate that the neuropeptides sauvagine and TRH differently control POMC biosynthesis in the Xenopus intermediate pituitary. This differential regulation is not only apparent with regard to time aspects (sauvagine has a sustained regulatory function, whereas TRH is only effective in the initial phase of POMC biosynthesis stimulation), but also an uncoupling of biosynthetic and release processes could be shown for TRH, which did not occur with sauvagine.

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Differential action of secreto-inhibitors on proopiomelanocortin biosynthesis in the intermediate pituitary of Xenopus laevis.

Cited by 22 publications

References 14 publications

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

Amphibian Melanotrope Subpopulations Respond Differentially to Hypothalamic Secreto-Inhibitors

Physiologically Induced Fos Expression in the Hypothalamo-Hypophyseal System of <i>Xenopus laevis</i>

Sauvagine and TRH Differentially Stimulate Proopiomelanocortin Biosynthesis in the <i>Xenopus laevis </i>Intermediate Pituitary

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