Secretion Of Melanocyte-stimulating Hormone Research Articles

Rapid growth of choroidal melanoma during pregnancy*

Editor, A 29-week pregnant, 31-year-old woman presented with a superior juxtapapillary choroidal tumour (8 mm largest basal diameter (LBD) × 5 mm height) in her left eye with a visual acuity of 20/30 (Fig. 1A, B). The patient wanted to delay any treatment until delivery. Three months later (2 weeks after delivering a boy), the tumour size had increased to 13 mm × 12 mm. There was extensive serous retinal detachment and subretinal haemorrhage that reduced her visual acuity to detecting only hand motion (Fig. 1C, D). Pathology of enucleated eye confirmed choroidal melanoma of mixed cell type and fluorescence in situ hybridization for chromosome 3 indicated monosomy (ZytoVision, Bremerhaven, Germany). Immunohistochemistry indicated absence of both oestrogen (Thermo Scientific, SP1, 1:100) and progesterone receptors (Dako, PgR 636, 1:100). The mean microvascular density (MVD) from three most highly vascularized areas (CD34+) was 79 vessels/0.313 mm2. Using standard photographs for semiquantitative scoring system (Makitie et al. 2001), macrophage density (CD68+) was determined to be moderate. (A) Fundus photography of the left eye depicting a superior juxtapapillary choroidal mass with associated serous retinal detachment. (B) Ultrasonographic image of the tumour with medium internal reflection. The largest basal diameter (LBD) was 8 mm, and the height was 5 mm. (C) Fundus photography of the same eye taken 3 months later. Tumor size increased with the development of extensive serous retinal detachment and subretinal haemorrhage. (D) Ultrasonographic image of the enlarged tumour with 13 mm in LBD and 12 mm in height. Hyperreflective layer indicated by arrowhead represents subretinal haemorrhage. We suspected that male foetal cells from the maternal circulation participated in tumour angiogenesis; however, there was no Y chromosome detected in the tumour using a DNA quantification kit (Applied Biosystems, Foster city, CA, USA). The patient was monitored for 2 years and remains metastasis free. We assumed that the LBD represented both tumour length and width. Although it could have been coincidental, the growth of UM during pregnancy have been previously reported (Seddon et al. 1982), as has transformation of clinically stable choroidal nevus into melanoma during pregnancy (Shields et al. 1991). Despite suspicions that increased growth was the result of endocrine effects, we did not detect oestrogen or progesterone receptors, which is consistent with previous studies (Seddon et al. 1982). In addition to rising oestrogen and progesterone, secretion of melanocyte-stimulating hormone (MSH) also increases during pregnancy. MSH is responsible for hyperpigmentation in pregnant women, usually affecting the nipples, areola, and face. UM is of melanocytic origin, so it has the potential to respond to elevated MSH. During pregnancy, immunity is altered to favour type 2 helper cell pathway (Th2) over type 1 helper cell pathway (Th1)to tolerate the foetus. This Th1/Th2 imbalance could promote rapid tumour growth. Vascular changes are frequently observed during pregnancy because of increased blood volume and raised angiogenic factors from high demand of vascular placenta. Although these vascular changes can merely increase tumour oedema or subretinal exudation, they can promote tumour vascularity as well, which facilitates growth. MVD was relatively high in our case, considering median MVD of 40 vessels/0.313 mm2 for 134 UM in one series (Makitie et al. 1999). Tumour vascularity is also affected by foetal cell microchimerism; foetal progenitor cells can enter the maternal circulation, and a recent study reported that these cells engraft in maternal cutaneous melanoma and differentiate into endothelial cells (Nguyen Huu et al. 2009). However, we did not detect foetal cells in the tumour. Therefore, the mechanism for rapid growth of UM in our patient may be multifactorial, relating to complex endocrine signalling, altered immunity, and a favourable angiogenic environment. The cumulative mortality rate depends on the tumour size. We recommend that a newly diagnosed UM in pregnant state be re-examined in one month if the tumour is to be observed. Initiation of the treatment is warranted in rapidly enlarging tumours. Part of this work was presented at the International Congress of Ocular Oncology conference from the 8–12th of September 2009 in Cambridge, United Kingdom.

Potassium-Induced Secretion of Melanocyte-Stimulating Hormone from the Melanotrophs of the Neurointermediate Lobe of the Lizard Anolis carolinensis

Secretion of melanocyte-stimulating hormone (MSH) from the melanotrophs of the neurointermediate lobe (NIL) of the lizard Anolis carolinensis was studied to investigate the role of membrane potential and extracellular calcium ions in the control of secretion in this species. MSH secretion was monitored from perifused NILs which had been in organ culture for 7–14 days prior to experiment to allow the nerve terminals present in the tissue to degenerate. Elevation of the K+ concentration in the perifusate induced a marked increase in MSH secretion. Perifusion of the cultured NILs with a nominally Ca-free solution did not reduce basal MSH secretion but blocked K-induced secretion. Moreover, nimodipine, an antagonist of voltage-gated Ca2+ channels, inhibited K-induced secretion, whereas BAY K 8644, a Ca2+ channel agonist, potentiated it; but neither drug affected basal secretion. High [K+] perifusate also stimulated MSH secretion from freshly excised (acute) NILs. Furthermore, in these preparations nominally Ca-free solution reduced basal secretion by 40% in addition to blocking K-induced secretion. As in the cultured NILs, nimodipine blocked and BAY K 8644 potentiated K-induced secretion in the acute NILs while not affecting basal secretion. The results from the cultured NILs are consistent with the hypothesis that stimulated MSH secretion from the melanotrophs of the anole is dependent upon Ca2+ influx through voltage-gated calcium channels. The qualitatively similar results obtained from the acute NILs in response to high [K+], nimodipine, and BAY K 8644 suggest that, for the most part, what is being observed are the direct effects of these substances on the melanotrophs. Basal secretion of MSH in cultured NILs is significantly less than that in the acute preparations. The calcium-sensitive fraction of basal secretion present in acute NILs may require the presence of nerve terminals.

Involvement of Protein Kinase C and Protein Tyrosine Kinase in Thyrotropin-Releasing Hormone-Induced Stimulation of -Melanocyte-Stimulating Hormone Secretion in Frog Melanotrope Cells

Involvement of Protein Kinase C and Protein Tyrosine Kinase in Thyrotropin-Releasing Hormone-Induced Stimulation of -Melanocyte-Stimulating Hormone Secretion in Frog Melanotrope Cells

Involvement of protein kinase C and protein tyrosine kinase in thyrotropin-releasing hormone-induced stimulation of alpha-melanocyte-stimulating hormone secretion in frog melanotrope cells.

We have previously shown that the stimulatory effect of TRH on alpha-MSH secretion from the frog pars intermedia is associated with Ca2+ influx through voltage-dependent Ca2+ channels, activation of a phospholipase C and mobilization of intracellular Ca2+ stores. The aim of the present study was to investigate the contribution of protein kinase C (PKC), adenylyl cyclase (AC), Ca2+/calmodulin-dependent protein kinase II (CAM KII), phospholipase A2, and protein tyrosine kinase (PTK) in TRH-induced alpha-MSH release. Incubation of frog neurointermediate lobes (NILs) with phorbol 12-myristate-13-acetate (24 h), which causes desensitization of PKC, or with the PKC inhibitor NPC-15437, reduced by approximately 50% of the effect of TRH on alpha-MSH release. In most melanotrope cells, TRH induces a sustained and biphasic increase in cytosolic Ca2+ concentration ([Ca2+]i). Preincubation with phorbol 12-myristate-13-acetate or NPC-15437 suppressed the plateau phase of the Ca2+ response. Incubation of NILs with TRH (10(-6) M; 20 min) had no effect on cAMP production. In addition, the AC inhibitor SQ 22,536 did not affect the secretory response of NILs to TRH. These data indicate that the phospholipase C/PKC pathway, but not the AC/protein kinase A pathway, is involved in TRH-induced alpha-MSH release. The calmodulin inhibitor W-7 and the CAM KII inhibitor KN-93 did not significantly reduce the response to TRH. Similarly, the phospholipase A2 inhibitors quinacrine and 7-7'-DEA did not impair the effect of TRH on alpha-MSH secretion. The PTK inhibitors ST638 and Tyr-A23 had no effect on TRH-induced [Ca2+]i increase but inhibited in a dose-dependent manner TRH-evoked alpha-MSH release (ED50 = 1.22x10(-5) M and ED50 = 1.47x10(-5) M, respectively). Taken together, these data indicate that, in frog melanotrope cells, PKC and PTK are involved in TRH-induced alpha-MSH secretion. Activation of PKC is responsible for the sustained phase of the increase in [Ca2+]i, whereas activation of PTK does not affect Ca2+ mobilization.

Secretion of Melanocyte-Stimulating Hormone and Adrenocorticotropin from Transplanted Pituitary Pars intermedia in Stressed and Nonstressed Rats

Rats bearing kidney grafts of the pituitary pars intermedia were divided into three groups: unstressed, acutely stressed, and chronically stressed. Corresponding sham-operated rats were used for comparisons. Twenty days after grafting, the rats were sacrificed and alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotropin (ACTH), and corticosterone were estimated in plasma. The adrenal/body weight ratio and DNA content of the glands were also investigated. The following results were obtained: MSH was found not to be increased in unstressed rats, but it was in grafted animals subjected to acute and chronic swimming stress. ACTH and corticosterone rose in all three groups. Adrenal/body weight ratio and DNA content increased only in grafted chronically stressed rats. Moreover, plasma corticosterone was found higher in grafted hypophysectomized rats than in non-grafted hypophysectomized animals. Administration of ergocryptine to nonstressed grafted rats induced a decrease in the blood content of ACTH and MSH, indicating that the grafts were the source of a part of the circulating ACTH. On the other hand, the fall in MSH levels could show the effect of the drug upon the pars intermedia. Comparison of the ratios of both hormones released in incubations showed that grafts secreted more ACTH than MSH; on the other hand, when intact neurointermediate lobes were incubated, MSH predominated over ACTH. For the first time it is demonstrated that the pars intermedia can secrete ACTH in vivo. Nevertheless, the ability to secrete this hormone is not a property of normal intact pars intermedia, but it manifests in the transplantations probably due to the overactivity of light cells induced by chronic stoppage of dopaminergic inhibition.

Spontaneous Spiking Activities of Porcine Pars intermedia Cells: Effects of Thyrotropin-Releasing Hormone

The electrophysiological properties of porcine melanotrophs in primary culture were studied with patch clamp techniques. In the cell-attached (c/a) configuration, extracellular spikes were recorded but in only 47 of the 259 cells examined; active cells were more frequently found in short-term cultures (48 h, 22 out of 71). In the whole-cell (WCR) configuration, the mean resting potential was -46.6 mV and the mean input resistance 2.41 G omega. In the current clamp mode, of the 99 cells recorded, 39.4% displayed spontaneous spiking activities, 14.1% spiked when a depolarizing current was applied, and 46.5% were silent. Two patterns of spontaneous activity were recorded. The first consisted of rapid membrane depolarizations (mean duration: 16.0 ms) which reached a mean value of +8.9 mV. These action potentials occurred either at random intervals or at a mean frequency of 1.19 Hz. Tetrodotoxin (TTX), a sodium channel blocker, completely abolished these action potentials. The second pattern consisted of regular bursts (mean duration: 1.69 s and mean frequency: 0.15 Hz) of spikes with smaller amplitudes (culminating at -9.5 mV) and greater durations (79.7 ms). This pattern could be recorded in the presence of TTX in the external medium. In the c/a configuration, thyrotropin-releasing hormone (TRH) and (3Me-His2)-TRH enhanced spike frequency, whereas histidyl-proline-diketopiperazine, a metabolite of TRH, had no effect. In WCR, out of the 27 cells tested, TRH (5.10(-9)-5.10(-8) M) induced firing in 4 quiescent cells and increased the frequency of action potentials in 4 spontaneously active cells. This was usually, but not necessarily, preceded by a hyperpolarization (n = 5). TRH (5.10(-8) M) enhanced the secretion of melanocyte-stimulating hormone (alpha MSH) from perfused isolated melanotrophs by 62.8 +/- 9.8% (n = 9) over basal levels. (3Me-His2)-TRH and (Pro3)-TRH mimicked the TRH response, whereas histidyl-proline-diketopiperazine was without effect.

GABAergic regulation of melanocyte-stimulating hormone secretion from the pars intermedia of Xenopus laevis: immunocytochemical and physiological evidence.

alpha-MSH secretion from the amphibian pars intermedia is under inhibitory hypothalamic control, and the catecholamine dopamine is thought to be the physiological MSH release-inhibiting factor. In the present study we evaluated the possible role of the neurotransmitter gamma-aminobutyric acid (GABA) in the regulation of the pars intermedia of Xenopus laevis. Immunocytochemical staining with antibodies to glutamic acid decarboxylase showed the presence of a rich GABAergic network in the intermediate lobe of the pituitary gland. Administration of GABA to superfused neurointermediate lobes caused a rapid and dose-dependent inhibition of basal release of MSH and immunoreactive endorphin. Pulse-chase experiments revealed that GABA gave a coordinate inhibition of the release of all peptides derived from proopiomelanocortin. In vivo administration of GABA resulted in almost complete pigment aggregation in dermal melanophores of both adults and larvae. Altogether, our results indicate that GABA is a physiologically important factor for regulation of the pars intermedia in Xenopus laevis.

Effects of veratridine, tetrodotoxin and other drugs that alter electrical behaviour on secretion of melanocyte-stimulating hormone from melanotrophs of the pituitary pars intermedia

Since melanotrophs are electrically active and exhibit spontaneous Na spikes, a study was made of the effects, on melanotroph secretion, of drugs known to influence electrical properties. The output of melanocyte-stimulating hormone was measured from perifused neurointermediate lobes of mice or melanotrophs dispersed from such lobes of mice or rats. Veratridine (200 μM), which is known to increase Na permeability in a variety of cells, caused a large, although transient, increase in secretion from the melanotrophs that required extracellular Ca 2+ and was blocked by the Na-channel blocker tetrodotoxin (1μM). Tetraethylammonium (10 mM), which blocks K channels and thus prolongs the duration of the action potential in many cells, also stimulated secretion in the melanotrophs in a Ca-dependent manner. This response was not, however, blocked by tetrodotoxin, and is thus not attributable to prolongation of Na spikes in these cells. Moreover, tetrodotoxin did not inhibit basal secretion. The stimulant effect of veratridine on secretion in melanotrophs and its suppression by tetrodotoxin suggests that voltage-dependent Na channels can participate in the regulation of hormone output in these cells of the pituitary pars intermedia. However, the apparent lack of effect of tetrodotoxin on basal secretion suggests that the spontaneous Na spikes previously observed in these cells are not required for promoting the Ca influx which other evidence shows is important for basal secretion.

Secretagogue effect of barium on output of melanocyte-stimulating hormone from pars intermedia of the mouse pituitary.

Ba ions caused an intense and prolonged discharge of melanocyte-stimulating hormone (MSH) from perifused neurointermediate lobes of mouse pituitaries and dispersed pars intermedia cells. The effect persisted in chronically cultured lobes or cells. It did not require Ca, but, like the Ca-dependent response to excess K, was blocked by cyanide combined with glucose lack. The secretagogue effect of Ba was blocked or prevented by Co or by excess Ca, both of which can reduce inward Ba currents through Ca channels. Prior exposure to excess K partially reduced the secretagogue effect of Ba, suggesting that depolarization caused some inactivation of Ba current. In contrast to Ba, excess K elicited secretion that was transient, and prior exposure of preparations to excess K (in the absence of Ca) profoundly suppressed the secretagogue effect of Ca. The evidence is consistent with the view that inward Ca current rapidly inactivates in these cells. It is concluded that Ba ions have a potent and persistent direct secretagogue effect on the melanotrophs that may reflect, in part, their ability to penetrate Ca channels more easily than Ca ions. The strong secretagogue effects of Ba on melanotrophs may be of considerable utility in studies on MSH secretion since a physiological secretagogue has yet to be discovered. Moreover, since the responses of melanotrophs (and other endocrine cells) to Ba can be distinguished from those of various other secretory cells and neurones, it is suggested that Ba may provide a tool for characterizing the distinctive membrane properties of the Ba-responsive endocrine cells.

GABA acts directly on cells of pituitary pars intermedia to alter hormone output.

Recent immunohistochemical evidence from the rat, indicating that gamma-aminobutyric acid (GABA)-containing fibres of central nervous origin project to the pars intermedia of the pituitary1,2, prompts inquiry into the function of this innervation. There is electrophysiological evidence that GABA acts directly on melanotrophs isolated from rat, through bicuculline-blockable receptors, to increase Cl- conductance and thereby drive the membrane potential towards the Cl- equilibrium potential in these cells, resulting in depolarization at rest or reduction of the depolarization caused by excess K+ (ref. 3). As voltage-dependent Ca channels can participate in the regulation of secretion in these cells4, we have now examined the effect of GABA on hormone output and find that it first stimulates and then inhibits spontaneous secretion of melanocyte-stimulating hormone (MSH) and inhibits K+-evoked secretion. Moreover, our pharmacological evidence suggests that similar receptors are involved in the secretory and the electrophysiological responses. A function of the GABAergic innervation may therefore be to regulate hormone output by acting directly on the melanotrophs, and this regulation may be affected by the changes in electrical properties induced by GABA.

Corticotropin-releasing factor stimulates secretion of melanocyte-stimulating hormone from the rat pituitary.

Administration of synthetic ovine corticotropin-releasing factor led to rapid, parallel increases in adrenocorticotropin and alpha-melanocyte-stimulating hormone concentrations in rat plasma. Prior treatment with dexamethasone almost completely blocked the adrenocorticotropin response but not the increase in melanocyte-stimulating hormone. These data demonstrate that corticotropin-releasing factor is a potent stimulator not only of adrenocorticotropin secretion from the corticotrophs of the anterior pituitary gland but also of peptide secretion from the intermediate lobe. Such data suggest that melanocyte-stimulating hormone and beta-endorphin play a role in the physiological response to stress.

Development of a radioimmunoassay for Pro-Leu-Gly-NH 2 (PLG or MIF-I): Evidence that PLG is not present in rat brain

Pro-Leu-Gly-NH 2 (PLG), which is the C-terminal tripeptide tail of oxytocin, has been reported to possess melanocyte-stimulating hormone (MSH)-release-inhibiting activity. Although it has been isolated from bovine hypothalamus, little is known about the CNS distribution of this peptide in other species. In this report, we describe the development of a radioimmunoassay which can be used to measure both PLG and oxytocin following chromatographic separation by high pressure liquid chromatography (HPLC). Using this method, we are unable to demonstrate the presence of any endogenous PLG in rat hypothalamus, preoptic area, pituitary, or eye tissue. However, synthetic PLG, which is added to tissue homogenates as an internal standard, is consistently recovered from all areas. We conclude that the PLG tripeptide is not present in the rat brain and thus cannot be the physiological regulator of MSH secretion.

Interaction of beta-endorphin, naloxone and dopamine: effects on melanocyte-stimulating hormone secretion of amphibian pituitaries in vitro.

Neurointermediate lobes from amphibians (Rana pipiens) were incubated in Medium 199 containing dopamine, beta-endorphin or dopamine plus beta-endorphin. Dopamine inhibited melanocyte-stimulating hormone (MSH) secretion as measured by bioassay in hypophysectomized frogs, an effect which was transiently reversed by beta-endorphin. The effects of endorphin were in turn partially suppressed by the opiate antagonist, naloxone hydrochloride. Cells treated with all three agents exhibited expanded rough endoplasmic reticulum and decreased secretory granule content, indicative of peptide release and new synthesis. Beta-Endorphin alone did not stimulate MSH secretion above control levels, and at one time period was seen to reduce MSH secretion. The findings indicate a complex interaction between beta-endorphin and dopamine directly upon MSH secretion at the level of the neurointermediate lobe.

Potassium-induced secretion of melanocytestimulating hormone from isolated pars intermedia cells signals participation of voltage-dependent calcium channels in stimulus-secretion coupling

The recent discovery of action potentials with a Ca component in pars intermedia cells raised the question whether voltage-dependent Ca 2+ influx participates in stimulus-secretion coupling in these cells. To test this, a study was made of the effects of a depolarizing concentration of K + on melanocyte-stimulating hormone (MSH) output from isolated pars intermedia cells of rats and mice obtained by tissue disaggregation and maintained in culture for periods ranging from 2 h to 10 days. The cells were placed in a column which was perfused thereby permitting continuous monitoring of MSH output. The cells secreted MSH promptly upon exposure to 50 m M K + and this effect was abolished when Ca 2+ was omitted or when Co 2+ was added to block Ca channels. It is concluded that activation of voltage-dependent Ca channels in pars intermedia cells allows influx of Ca ions that provides an adequate stimulus for MSH secretion. Furthermore, inhibitory effects of Ca 2+ lack and of Co 2+ addition on basal MSH output suggest the operation of such a Ca-dependent mechanism during spontaneous secretory activity. Secretory responses to high [K +], although intense, were brief and waned rapidly during continuous exposure to K +. Experiments showing that Ca 2+ fails to elicit secretion when introduced with a delay of several minutes after exposure to high [K +] indicate that the transience of the response is due to inactivation of voltage-dependent Ca channels. The brevity of the response of the isolated pars intermedia cells to high [K +] may explain, at least in part, why stimulant effects of excess K + have not been seen previously, or in the present experiments in intact neurointermediate lobes of rats. When the much smaller, and seemingly more favorable, neurointermediate lobes of mice were used, K + elicited a Ca-dependent secretion of MSH comparable with that seen in the isolated cells. The demonstration that pars intermedia cells respond directly to a depolarizing stimulus by secreting MSH encourages the view that electrical activity in these cells is involved in the regulation of secretion.

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

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.

Action potentials in gland cells of rat pituitary pars intermedia: inhibition by dopamine, an inhibitor of MSH secretion.

1. Cells were dissociated from rat pituitary pars intermedia, maintained in culture, and subjected to electrophysiological study.2. Recorded membrane potentials varied widely (range - 18 to about - 80 mV). They were relatively insensitive to changes in external Na but were rapidly and reversibly lowered by excess K.3. Action potentials were elicited by passing current through intracellular recording electrodes. They were reversibly blocked by tetrodotoxin (TTX, 2 x 10(-6)M) or by removal of Na from the recording solution and thus appeared to be Na spikes. Cells yielding action potentials in response to depolarization had relatively high membrane potentials (about - 65 mV) which may be representative of the true resting membrane potential of pars intermedia cells.4. Spontaneous action potentials were recorded extracellularly from nearly all the many isolated pars intermedia cells studied with a microsuction electrode. Their amplitude was reduced by TTX (0.1-2 x 10(-6)M). Electron microscopic examination of cells producing action potentials showed them to be hormone-containing parenchymal (gland) cells.5. Dopamine (10(-6)M), a presumed physiological inhibitor of secretion of melanocyte stimulating hormone (MSH) from pars intermedia cells, decreased the frequency of spontaneous action potentials but not their amplitude. Similar effects were seen with noradrenaline (10(-6)M), another inhibitor of MSH secretion, whereas isoprenaline and 5-hydroxytryptamine (5-HT), which do not inhibit MSH secretion, had no effect.6. Action potentials may be involved in stimulus-secretion coupling in pars intermedia cells.

Differences in the release of melanocyte-stimulating hormone in vitro by rat pituitary glands collected at various times during the oestrous cycle.

The release of melanocyte-stimulating hormone (MSH) into the medium during incubation and the pituitary tissue content of MSH were measured separately using pituitary glands collected from rats at various stages of the oestrous cycle. The MSH was measured by a biological assay using a synthetic alpha-MSH as standard. The release of MSH was maximal during thepro-oestrous phase and MSH content of the pituitary gland was highest during dioestrus. The influences of the tripeptide Pro-Leu-Gly-NH2, which inhibits MSH secretion in vivo, and of progesterone on the release of MSH in vitro were studied with tissue collected at various phases of the oestrous cycle. Pro-Leu-Gly-NH2 was effective in inhibiting MSH release both at pro-oestrus and oestrus but not at dioestrus. Progesterone overcame this inhibition.

Immunoreactive alpha-MSH in human plasma in pregnancy.

IT has been suggested that the increased skin pigmentation of pregnancy is due to increased secretion of melanocyte-stimulating hormone (MSH) (refs 1–3), but this is not β-MSH, because the slight increase in immunoreactive β-MSH found in late pregnancy4 is much less than the changes associated with skin pigmentation. Evidence suggests that the 22 amino acid β-MSH, originally thought to be the major MSH in man5, is an extraction artefact6, and the immunoreactive β-MSH measured in the human4,7,8 is in fact β or γ lipotrophin9. Other forms of β-MSH have never been isolated from the adult human pituitary and only small quantities of α-MSH have been found10. Immunoreactive α-MSH is present in larger amounts in the human foetal pituitary11 and has also been detected in the pituitary of the pregnant woman12. We report here the presence of circulating immunoreactive α-MSH in pregnancy.

Pars intermedia electrical potentials: changes in spike frequency induced by regulatory factors of melanocyte stimulating hormone (MSH) secretion.

Spontaneous action potentials recorded from pars intermedia (PI) cells of frog pituitaries are correlated with spontaneous melanophore stimulating hormone (MSH) secretion from that gland. Those agents known to induce hormone release (e.g., serotonin, isoproterenol) increase the rate of electrical activity, whereas those which inhibit secretion (e.g., norepinephrine, dopamine, GABA) reduce the frequency of spikes. MSH secretion appears to involve cellular depolarization while inhibition of release is associated with cell membrane polarization.

Pars Intermedia ACTH and MSH Content: Effect of Adrenalectomy, Gonadectomy and a Neurotropic (Noise) Stress

Pars intermedia (PI) ACTH and melanocyte-stimulating hormone (MSH) content and pars distalis (PD) ACTH concentration were measured following 3 experimentally induced 'perturbations'. The feedback-induced increase in ACTH release following adrenalectomy is not accompanied by a change in PI ACTH and MSH contents, while the feedback-induced increase in gonadotropin secretion following gonadectomy is associated with significant changes in PI ACTH and MSH contents. A well-defined neurotropic (noise) stressor resulted in significant increases in PI ACTH and MSH. A striking finding in all of the studies was a positive correlation between PI ACTH and MSH contents. We conclude that PI ACTH and MSH secretion are altered with feedback-induced alterations in gonadotropin secretion and with neurotropic stressors.