Corticotropin-like Intermediate Peptide Research Articles

Distribution of the pro-opiomelanocortin-immunoreactive axons in relation to the serotoninergic neurons in the dorsal raphe nucleus of the rat.

The anatomical relationships between pro-opiomelanocortin-containing axons and serotonin neurons in the nucleus raphe dorsalis (NRD) of the rat were examined at the light microscope level with antibodies against CLIP (corticotropin-like intermediate lobe peptide), alpha-MSH (alpha-melanocyte-stimulating hormone) and serotonin. Sequential double labeling was performed with either immunofluorescence or peroxidase-antiperoxidase techniques. It was observed that the network of POMC-immunoreactive axons displayed a gradient of decreasing density from rostral to caudal levels and from dorsal to ventral parts or the NRD. The examples of close proximity between immunoreactive axons and serotonin cell bodies or dendrites were rather scarce. On the whole, the immunoreactive fibers seemed to run quasi-independently of the serotonin neurons.

Immunohistochemical distribution of corticotropin-like intermediate lobe peptide (CLIP) immunoreactivity in the human brain

The immunocytochemical distribution of CLIP (corticotropin-like intermediate lobe peptide) or ACTH (18–39), a small biologically active peptide, was examined in the human brain, using a monoclonal antibody against this peptide. Groups of CLIP-immunoreactive cell bodies, small to medium size and bipolar or triangular in shape, were found in the basal hypothalamus extending from the retrochiasmatic region to the premammillary nuclei area. Immunoreactive fibers with varicosities, terminals and “pipe shape” structures, were distributed within the hypothalamus, limbic structures, the brainstem and spinal cord nuclei, forming a particularly rich network in the hypothalamus, the preoptic area, the septal region, the amygdala and the upper brainstem periaqueductal gray matter. The above neuroanatomical observations confirm and extend previous findings in animals, strengthening even more the possibility that this peptide may be involved in numerous behavioral, autonomic and physiological functions such as regulation of sleep-waking cycle, pain control and respiratory and cardiovascular regulation.

Proopiomelanocortin gene and gene products: A comparative study

The beneficial effects of morphine, mainly euphoria and analgesia, have been known for several centuries. However, it is only twenty years ago that the story of endogenous opioid peptides started. In 1971, Goldstein and collaborators established the existence of receptors to morphine within the brain (Goldstein et al., 1971). The discovery of the numerous endogenous ligands of these receptors began in 1974 (Terenius and Wahlstrom, 1974). After these first and somewhat hesitating steps, the tale of opioids has been written extremely quickly. The main opioid peptides, beta-endorphin, Met-enkephalin, Leu-enkephalin, and the dynorphins, are today established to derive from three large precursors. Proopiomelanocortin (POMC), proenkephalin and prodynorphin were cloned and sequenced within a few years (Nakanishi et al., 1979; Noda et al., 1982; Kakidani et al., 1982). These three precursors are all large prohormones processed into several biologically active peptides, these being separated by pairs of basic amino-acid residues. Proopiomelanocortin, precursor of betaendorphin, is probably the most studied of these three molecules. It was first shown to be expressed in the pituitary, both in the corticotroph cells of the anterior lobe, where it is mainly processed into adrenocorticotropin (ACTH) and beta-lipotropin (BLPH), and in the melanotroph cells of the intermediate lobe, where it is cleaved into alphamelanocyte stimulating hormone (AMSH), corticotropin-like intermediate lobe peptide (CLIP), gamma-lipotropin (GLPH) or betamelanocyte stimulating hormone (BMSH) and beta-endorphin (BEnd). Although they were first supposed to be only expressed in nervous tissues, POMCderived peptides have been observed in many non-pituitary tissues such as the reproductive tract (Tsong et al., 1982), gastrointestinal tract, kidney, liver and heart (Saito and Odell, 1983; DeBold et al., 1988). They are also synthesized in several cells of the immune system (DiAugustine et al., 1980; Smith and Blalock, 1981; LacazeMasmonteil et al., 1987; Lolait et al., 1986) and constitute for this reason important common signal molecules of the neuroendocrine and the immune systems.

CRF, Urotensin I, and sauvagine stimulate the release of POMC-derived peptides from goldfish neurointermediate lobe cells

In teleost fishes, the melanotropes of the neurointermediate lobe of the pituitary gland release numerous peptides—adrenocorticotropin (ACTH), melanotropin (MSH), lipotropin (LPH), corticotropin-like intermediate lobe peptide (CLIP), and endorphin—which are derived from the precursor molecule proopiomelanocortin. Superfused, isolated, dispersed goldfish neurointermediate lobe cell columns were used to investigate the release of immunoreactive (ir) α-MSH and ir ACTH from goldfish melanotropes. Stimulation of neurointermediate lobe cell columns with pulses of the structurally homologous peptides, Catostomus urotensin I (UI), ovine corticotropin-releasing factor (oCRF), or sauvagine, produced a significant increase in the concomitant release of ir α-MSH and ir ACTH. UI was two to three times as potent as ovine CRF or sauvagine. These studies suggest that CRF- and UI-like peptides stimulate the secretory activity of teleost melanotropes.

Immunocytochemical location of pituitary cells containing ACTH, α-MSH, and β-endorphin in Acipenser transmontanus, Lepisosteus spatula, and Amia calva

This immunocytochemical study of the pituitaries of the primitive actinopterygians, Acipenser transmontanus, Lepisosteus spatula, and Amia calva, showed a strict delineation between the hormonal fragments of proopiomelanocorticotropin (POMC) produced by corticotropes of the pars distalis and the melanotropes of the pars intermedia. Corticotropes were immunoreactive only for ACTH and not to either of the further degradation products, α-MSH or β-endorphin. Melanotropes were shown to be immunoreactive to all three antisera but it is argued that immunoreactivity of melanotropes to ACTH antiserum is due to that antiserum's cross-reactivity with the cleavage product corticotropin-like intermediate peptide. The PAS positivity of both the corticotropes and the melanotropes of all three primitive fish argues for an ancient origin of a carbohydrate component of POMC and for its loss or reduction in teleosts where these cells are PAS negative.

Isolated Adrenocorticotropin Deficiency Associated with an Autoantibody to a Corticotroph Antigen That Is not Adrenocorticotropin or Other Proopiomelanocortin-Derived Peptides*

A 44-yr-old man with hypocortisolism was shown to have an undetectable basal plasma ACTH level and absent or subnormal ACTH and beta-lipotropin responses to provocative testing with insulin, vasopressin, and CRH. Endocrine function after glucocorticoid replacement was otherwise normal, thus establishing the diagnosis of isolated ACTH deficiency. This patient's serum was tested immunohistochemically for the presence of an antipituitary antibody by indirect immunofluorescence of rat pituitary tissue. Positive immunostaining was observed in stellate-shaped cells in the anterior and intermediate lobes. Immunopositive cells were shown by immunoelectron microscopy to have ultrastructural characteristics of corticotrophs. Immunoreactivity was concentrated in secretory granules 120-170 nm in diameter. In a double immunolabeling procedure, staining by the patient's serum was shown to colocalize with rabbit antiserum to ACTH, but not with antisera to PRL, GH, beta TSH, or beta LH. Immunoabsorption of the patient's serum with ACTH-(1-24), ACTH-(1-39), gamma MSH, corticotropin-like intermediate lobe peptide, beta-endorphin, or beta-lipotropin failed to diminish immunolabeling in the pituitary. We conclude that the antipituitary antibody in this patient's serum shows immunohistochemical specificity for a rat corticotroph antigen located in secretory granules that is neither ACTH nor any of the proopiomelanocortin (POMC)-derived peptides tested. The autoantigen could be a cell-specific granular factor involved in the posttranslational processing of POMC or secretion of ACTH. We postulate that an autoimmune process may account for this patient's disease, and that his antipituitary antibody could play a pathogenic role by either inhibiting a POMC-processing enzyme or initiating an antibody-dependent cell-mediated cytotoxicity reaction, resulting in the selective destruction of corticotrophs.

Proopiomelanocortin (POMC)-derived peptides and sleep in the rat Part 1 — Hypnogenic properties of ACTH derivatives

The sleep-wake effects of the proopiomelanocortin (POMC)-derived peptides, i.c.v. injected, are reported. Adrenocorticotropic hormone (ACTH, 1 μg) induces an awakening effect, while its two derivatives, desacetyl-α-MSH (des-α-MSH, 1 ng) and corticotropin-like intermediate lobe peptide (CLIP, 10 ng), are respectively able to increase slow wave sleep (SWS) and paradoxical sleep (PS); the hypnogenic effect of CLIP is also observed in hypophysectomized rats. Furthermore, two hypothalamic factors known to be involved in the control of POMC derivatives were also injected; MSH Inhibiting Factor (MIF) does not influence the viligance states, while Corticotropin Releasing Factor (CRF, 1 μg) increases the waking state. Finally, some preliminary results, obtained with a restraint stress and suggesting a possible interrelation between stress, sleep and POMC derivatives, are discussed.

Proopiomelanocortin (POMC)-derived peptides and sleep in the rat Part 2 — Aminergic regulatory processes

Apomorphine (Apo), a D1 D2 Dopamine (DA) agonist, at high doses (500 μg/kg) induces a short-lasting insomnia, antagonized by a secondary injection of corticotropin-like intermediate lobe peptide (CLIP, 10 ng); these effects are also observed with hypophysectomized (hypoX) rats. The administration of the serotonin (5-HT) agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OHDPAT, 0.3 mg/kg) induces also an insomnia which, unlike Apo, is followed by a significant PS rebound. CLIP, again, antagonizes the 8-OHDPAT-induced insomnia. Finally, Bromocriptine (5 mg/kg), an agonist for both DA and 5-HT, induces first an insomnia (antagonized by CLIP), followed by a PS rebound; these effects persist in hypoX rats.

The Degradation of Bioactive Peptides and Proteins by Dipeptidyl Peptidase IV from Human Placenta

The degradation of several bioactive peptides and proteins by purified human dipeptidyl peptidase IV is reported. It was hitherto unknown that human gastrin-releasing peptide, human chorionic gonadotropin, human pancreatic polypeptide, sheep prolactin, aprotinin, corticotropin-like intermediate lobe peptide and (Tyr-)melanostatin are substrates of this peptidase. Kinetic constants were determined for the degradation of a number of other natural peptides, including substance P, the degradation of which has been described earlier in a qualitative manner. Generally, small peptides are degraded much more rapidly than proteins. However, the Km-values seem to be independent of the peptide chain length. The influence of the action of dipeptidyl peptidase IV on the biological function of peptides and proteins is discussed.

Neurotransmitters, neuropeptides and binding sites in the rat mediobasal hypothalamus: effects of monosodium glutamate (MSG) lesions

Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptide-containing neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-, and ENK-IR fibers were observed. The numbers of TH-, SOM- and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF- and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK- and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic hormone inhibits angiotensin II-stimulated inositol phosphate accumulation in rat adrenal glomerulosa cells

Rat adrenal glomerulosa cells labelled for 18 h with [ 3H]inositol responded to angiotensin II with a dose-dependent stimulation of the accumulation of inositol monophosphate, inositol bisphosphate and inositol trisphosphate. Addition of adrenocorticotropic hormone (ACTH) (10 −7 M) reduced the maximum responses without altering the EC 50 values for angiotensin II. Thus, ACTH acted as a non-competitive inhibitor with respect to angiotensin II. No inhibition was observed in cells labelled for 2 h with [ 3H]inositol. Detailed examination of the inhibition showed that ACTH(1–24) was the most potent inhibitor, with ACTH(1–39) being 10-fold less potent. A mixture of α-melanocyte-stimulating hormone (α-MSH) (ACTH(1–13)) and corticotropin-like intermediate lobe peptide (ACTH(18–39)) was similarly inactive. ACTH(5–24) did not produce detectable inhibition. In terms of specificity, the receptor mediating ACTH inhibition of phosphatidylinositol turnover was similar to the receptor which mediated stimulation of aldosterone synthesis. Inhibition by ACTH was additive with inhibition produced by dibutyryl cAMP demonstrating that it was not mediated by rises in intracellular cAMP. ACTH inhibition also was additive with inhibition by the calcium channel blocker, nifedipine. These results demonstrate an interaction between ACTH receptors and angiotensin II receptors in adrenal glomerulosa cells at the level of their receptor-second messenger pathways.

Down-regulation of proopiomelanocortin synthesis and beta-endorphin utilization in hypothalamus of morphine-tolerant rats

We investigated regulation of the dynamic state of enkephalin and endorphin brain stores during morphine tolerance and dependence using cDNA hybridization and radioimmunoassay of the biologically active peptide(s) and their respective peptide precursors. Rats were made tolerant to morphine with the subcutaneous implantation of three morphine pellets (75 mg each) for a period of five days. Hypothalamic proopiomelanocortin (POMC) mRNA, POMC, and corticotropin-like intermediate lobe peptide content were decreased by 50% in morphine-dependent rats. However, beta-endorphin content remained unchanged. Enkephalin and proenkephalin mRNA content in various brain structures failed to change. A single injection of naltrexone (2 mg/kg) 1 hour before decapitation did not reverse the decrease in POMC mRNA and POMC content elicited by morphine. However, a slower, spontaneous withdrawal caused by removal of the pellets did reverse (after two days) the down-regulation of the hypothalamic POMC system. A single injection of morphine (10 mg/kg) failed to affect any parameter used to assess the dynamic state of opioid peptides.

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

To examine whether the hypothalamic corticotropin-releasing hormone (CRH) neuron is regulated by CRH, by products of the proopiomelanocortin (POMC) gene, and/or by glucocorticoids, we used a rat hypothalamic organ culture system in which rat CRH secretion from single explanted hypothalami was evaluated by an RIA (iCRH) specific for rat CRH. The effects of graded concentrations of ovine CRH (oCRH), adrenocorticotropin hormone (ACTH), beta-endorphin (beta-EP), alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-like intermediate lobe peptide (CLIP), ovine beta-lipotropin (ovine beta-LPH), and dexamethasone (DEX) upon unstimulated and serotonin- (5HT), acetylcholine- (ACh), and norepinephrine-(NE) stimulated CRH secretion were determined. oCRH and DEX inhibited unstimulated iCRH secretion with ID50 at the 10(-8) M range. ACTH had no detectable suppressive effect at 10(-8) M. oCRH, ACTH, and DEX inhibited 5HT-, ACh-, and NE-stimulated iCRH secretion in a dose-dependent fashion. beta-EP, alpha-MSH, and CLIP also inhibited 5HT-induced iCRH secretion. Of the latter peptides, the strongest inhibitor was beta-EP and the weakest was CLIP. Ovine beta-LPH had only a weak inhibitory effect on 5HT-induced iCRH secretion. Generally, the concentrations required for 50% suppression of neurotransmitter-stimulated iCRH secretion were significantly lower than those required for a similar suppression of unstimulated iCRH secretion. In conclusion, these data suggest the presence of multiple negative feedback loops involved in the regulation of the hypothalamic CRH neuron: an ultrashort CRH-mediated loop, a short, hypothalamic POMC-derived peptide loop, and a long, glucocorticoid-mediated negative feedback loop. The potency of these negative feedback loops may be determined by the state of activation of the CRH neuron.

Distribution and colocalization of delta sleep inducing peptide (DSIP) with corticotropin-like intermediate lobe peptide (CLIP) in the human hypophysis

DSIP and CLIP [ACTH (18–39)] immunoreactive (IR) neurons and fibers were examined in the human hypophysis and pituitary stalk using immunmohistofluorescence and peroxidase-antiperoxidase methods. Double-stained and adjacent stained sections demonstrate that DSIP is colocalized in about 75% of CLIP-IR-like cells in the anterior pituitary and in residual intermediate lobe cells. Only few CLIP-IR-like fibers are observed in the posterior lobe. On the contrary, a high density of DSIP-IR fibers is visualized in the stalk. It is suggested that DSIP acts as a sleep promoting factor (one of many other actions) and that CLIP increases the paradoxical sleep, so that these two peptides could play a role in the regulating system of the sleep-waking cycle.

Post-translational processing of pro-opiomelanocortin (POMC)-derived peptides during fetal monkey pituitary development: I. Adrenocorticotropin (ACTH) and α-melanotropins (α-MSHs)

We have studied the post-translational processing of POMC-derived peptides during fetal monkey development using immunoassay and reverse-phase high-performance liquid chromatography (RP HPLC). Pituitary tissues obtained from fetal monkeys ranging from Gestational Day 50 to 155 were fractionated and analyzed for ACTH- and α-MSH-related peptides and compared to adult forms. Extracts of whole pituitary from Fetal Days 50 and 55 contained ACTH(1–39) and very small amounts of CLIP (corticotropin-like intermediate-lobe peptide; ACTH(18–39))-like immunoactivity. Acetylated α-MSHs were not detectable at Day 50. α-MSHs were barely detectable at Day 55. By Day 65, when pituitary lobes were separable, small amounts of des-, mono-, and diacetyl α-MSH were detectable in NIL extracts, but not in anterior lobe extracts. ACTH(1–39) levels were negligible when compared to increasing α-MSHs through Fetal Day 80 to 155 in the intermediate lobe. The CLIP immunoactivity was negligible in Day 80 and adult anterior lobe extracts. Thus, lobe-specific proteolytic processing of ACTH-related peptides was well established by midterm gestation. Marked increases of α- N- and α- N,O-acetylated forms of α-MSHs were detected during middle and late stage fetal development. Diacetyl α-MSH was the predominant form of α-MSH in adult NIL extracts. No acetylated α-MSHs were found in anterior lobe tissues, thus adult anterior lobe extracts contained almost exclusively ACTH(1–39). However adult NIL extracts contained two distinct forms of CLIP-related immunoactivity. Therefore changes in post-translational processing patterns of ACTH-related and α-MSH-related peptides continued to some extent, postnatally. These data indicate that marked changes in post-translational processing of POMC-derived ACTH-related products occur during the first half of monkey gestation.

Regulation of proopiomelanocortin gene expression in pituitary.

I. Introduction THE POMC gene encodes the complex precursor to a variety of biologically active, important neuromodulator and endocrine peptides. It is expressed in a variety of tissues in the mammal, but its main site of expression is the pituitary anterior lobe cortocotroph and intermediate lobe melanotroph. The POMC molecule is posttranslationally processed to different biologically active peptides in these two cell types, with ACTH, β-lipotropin, and β-endorphin being major products in the corticotroph and α-MSH, corticotropin-like intermediate lobe peptide, and acetyl-β-endorphin in the melanotroph (1). This array of different biological activities derived from the POMC molecule possibly necessitates the observed complex regulation of POMC peptide secretion and POMC gene expression in pituitary. Regulation of POMC peptide secretion has recently been reviewed in several places (2, 3). This review will deal primarily with the regulation of POMC gene expression in rat and mouse pituitary tissues, the sp...

Effect of androgens on hypothalamic pro-opiomelanocortin.

Testosterone and estradiol have been shown to affect the hypothalamic content of several pro-opiomelanocortin (POMC)-derived peptides in castrated male and female rats, respectively. It was unclear, however, whether the effects of testosterone on hypothalamic POMC were due to conversion by aromatization to estradiol or whether there were independent androgen actions on hypothalamic POMC. In order to answer this question, the effect of treatment with the nonaromitizable androgen 5-alpha-dihydrotestosterone (DHT) on the concentration of beta-endorphin (beta-EP) in the medial basal hypothalamus (MBH) was studied in castrated male rats and compared to the effect of treatment with testosterone or estradiol. The concentrations of two other POMC-derived peptides, corticotropin-like intermediate lobe peptide (CLIP) and alpha-MSH were measured as well. Adult male rats were castrated and received either no treatment or treatment with subcutaneously implanted silastic capsules, containing either DHT, testosterone or estradiol, designed to produce steroid levels in a physiological range. After 4 weeks the mean concentration of beta-EP in the MBH of the untreated castrated rats was 1,640 +/- 56 fmol/mg protein. This was reduced significantly to 1,184 +/- 74 fmol/mg protein after DHT treatment (p less than 0.001). Similar reductions to 1,340 +/- 95 and 1,130 +/- 85 fmol/mg protein were noted after testosterone and estradiol treatment, respectively. The mean CLIP concentration of 1,870 +/- 73 fmol/mg protein in the untreated animals fell to 1,390 +/- 95 after DHT (p less than 0.001) compared to 1,520 +/- 105 and 1,260 +/- 101 after testosterone and estradiol treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

S-100 protein in clonal astroglioma cells is released by adrenocorticotropic hormone and corticotropin-like intermediate-lobe peptide.

S-100 protein in clonal GA-1 and C6 rat glioma cell lines was released in serum-free medium supplemented with adrenocorticotropic hormone (ACTH). The induction of S-100 protein release by ACTH was dose-dependent, showing a half-maximal release at about 5 microM, and the S-100 protein concentration in the medium increased sharply within 3 min, but slightly during further incubation. The S-100 protein release was apparently accompanied by a decrease in the membrane-bound form of S-100 protein in the cell. The S-100 protein release was induced not by the ACTH1-24 fragment, which exhibits the known effects of ACTH, but by the ACTH18-39 fragment, which is designated as corticotropin-like intermediate-lobe peptide (CLIP). These results indicate that the C-terminal half of ACTH is responsible for the S-100 protein release. The enhancement of S-100 protein release by ACTH was also observed in normal rat glioblasts. The release induced by ACTH was apparently specific to S-100 protein, because little release of the cytoplasmic enzymes, creatine kinase, and enolase was observed under the same conditions. High concentrations (5 mM) of dibutyryl cyclic AMP or dibutyryl cyclic GMP were also found to induce S-100 protein release; however, catecholamines (epinephrine, norepinephrine, isoproterenol, and dopamine), acetylcholine, and glutamic acid did not enhance the release.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of POMC-derived peptides on aldosterone secretion in vivo.

1. To investigate a role for peptides derived from the precursor molecule pro-opiomelanocortin (POMC) on the control of aldosterone secretion (ASR), alpha-, beta-, gamma 1-, and gamma 2-melanocyte stimulating hormone (MSH), corticotropin-like intermediate lobe peptide (CLIP) or beta-endorphin were infused into the adrenal arterial supply of sheep with an adrenal cervical autotransplant. 2. None of the peptides had any significant effect on aldosterone secretion rate in Na replete, unstressed, conscious animals. In contrast, ACTH-stimulated ASR approximately twofold. 3. POMC-derived peptides other than ACTH appear to have little or no effect on the short-term control of aldosterone secretion in vivo, although a role in control and modulation of adrenal function over the longer term cannot be discounted.

Endocrine cells producing regulatory peptides.

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.