Melanocyte-stimulating Hormone Levels Research Articles

The color change and stress response of Atlantic salmon (Salmo salar L.) infected with Aeromonas salmonicida

Fish challenged with pathogens often show behavioral disorders. The present study investigated the influence of Aeromonas salmonicida infection on the body color changes of Atlantic salmon (Salmo salar L.). In both conditions of a white background and transfer from the black background to the white background, the body color contrast of the fish infected with A. salmonicida (100 μL bacterium solution 8.2 × 109 CFU ml−1 in the dorsal muscle) declined significantly following an initial increase compared with the control group (100 μL 0.9 % NaCl); the greatest differences were observed on day 11, at 57.6 % and 52.7 % respectively (P<0.01). In the black background (transferred from white to the black background), A. salmonicida infection resulted an initial lower and then higher contrast in the challenged fish (P<0.01), and the greatest difference occurred on day 5, reaching 156.7 % (P<0.01). Meanwhile, the cortisol, melanocyte stimulating hormone (MSH) and melanin-concentrating hormone (MCH) levels in serum were also evaluated. Comparing the infected fish with the control fish, the cortisol (7.2 % ∼ 21.2 %), MSH (25.8 % ∼48.6 %) and MCH (36.4 % ∼ 54.4 %) levels of the infected fish were elevated to varying degrees after infection with A. salmonicida (P < 0.05). The results suggested that A. salmonicida challenge altered the color-change behavior, which might be regulated by MSH and MCH.

Hypothesis: does adrenalitis caused by immune checkpoint-inhibitors put melanoma patients at an elevated risk for recurrence?

Primary adrenal failure (Addison’s disease) is a rare complication of immune checkpoint inhibitor (ICI) therapy. Untreated – and also sometimes under adequate hydrocortisone replacement therapy – the levels of ACTH (Adrenocorticotropic hormone) and MSH (Melanocyte stimulating hormone) are elevated. This may be a reason for concern in patients with malignant melanoma (MM): Melanocortin receptors bind to ACTH and the different isoforms of MSH. For example, the melanocortin 1 receptor (MC1R) is overexpressed in many human melanoma cells. Since it is also involved in the proliferation of melanoma cells, the elevated levels of ACTH and its proteolytic cleavage product α-MSH typical for primary failure may lead to an activation of the receptor and, thus, put MM patients that suffered from primary adrenal failure after ICI therapy at an elevated risk for recurrence or an unfavorable course of the disease. Novel dual-release hydrocortisone therapy results in lower ACTH (and most probably lower α-MSH) levels due to the more physiological mode of hydrocortisone release. Given that the concern raised in this hypothesis is confirmed in future investigations, patients who suffer from primary adrenal failure after ICI therapy may benefit from a dual-release hydrocortisone replacement regimen.

The effect of cadmium on plasma melanocyte-stimulating hormone and morphological changes of melanophores in the cichlid fish Oreochromis niloticus, at different salinity levels

ABSTRACTThe effects of cadmium concentration (0, 2.5 and 5 mg L−1) on melanocyte-stimulating hormone (MSH), melanophore index (MI), and melanophore number (MN), as well as a microscopic examination of scale melanocytes in tilapia (Oreochromis niloticus Linnaeus, 1757) was evaluated at different salinity levels (0, 5 and 15 ppt). The levels of MSH, MI, and MN were lower in Cd-exposed fish than in control fish (not exposed to Cd) at salinity level of 0 and 5 ppt. In ppt, however these levels of MSH, MI and MN in control and Cd-exposed fish were not significantly different. In the media without Cd, the levels of MSH, MI and MN were not significantly different at all salinities. The morphological changes of melanophores were higher in Cd-exposed fish than in control fish at salinity 0 and 5 ppt, respectively. These morphological changes were not significantly different in the control fish at all salinities as well as in fish exposed to 0–5 mg L−1 Cd at salinity of 15 ppt. This study therefore demonstrates that the toxic effect of Cd on MSH levels and melanophore morphology decreased with increasing salinity. Further, due to the sensitivity of chromatophores to Cd, melanophore morphology is proposed as a biomarker of Cd exposure in aquatic ecosystems.

Alopecia areata - hyperactivity of the hypothalamic-pituitary-adrenal axis is a myth?

Psychological stress is known to cause exacerbation of different skin pathologies including alopecia areata (AA). A hyperactivity of the hypothalamic-pituitary-adrenal axis (the HPA axis) in patients affected by AA (AA patients) was proposed to be a neuroendocrine response to stress. Still little is known about melanocyte-stimulating hormone (MSH) and cortisol production in AA settings. The aim of the study was to compare trends in a production of MSH and cortisol in patients with AA patients and healthy controls. Plasma concentrations of free cortisol and MSH were measured in 43 AA patients (35.5 ± 10.6 years) and 37 healthy subjects (35.9 ± 10.5 years) selected from the Dermatology Outpatient Clinic at Medical University of Silesia in Katowice, Poland. Results were submitted to statistical analysis with Shapiro-Wilk W-test and subsequently nonparametric (Mann-Whitney U-test) or parametric (Student's t-test) statistics were performed. Mean plasma level of MSH was 5.39 ng/mL in AA patients and 5.71 ng/mL in healthy controls. The difference between groups was non-significant (P = 0.435), but the control group manifested higher values of MSH (Q75 = 13.6 ng/mL vs Q75 = 5.98 ng/mL) and this tendency was especially stronger in females. AA patients had greater mean plasma level of cortisol (157.63 ± 91.16 µg/L) than healthy controls (123.32 ± 71.28 µg/L); however, the difference between them was also non-significant (P = 0.063). No sex-dependent tendency to a greater production of cortisol was found. Expectations of disturbances in production of MSH and cortisol were not fulfilled. Neither MSH nor cortisol plasma levels appear to be clearly changed in AA patients.

The increased incidence of malignant melanoma in obese individuals is due to impaired melanogenesis and melanocyte DNA repair

Obese individuals have a higher incidence of malignant melanoma (MM). We here suggest that the higher incidence is caused by a reduction of melanogenesis and a decreased capacity of melanocytes DNA repair. These effects are caused by an increase in the haematic levels of melanocyte stimulating hormone (MSH) antagonists, namely of the protein attractin, the melanocyte concentrating hormone (MCH), the agouti related protein (ASRP) and perhaps also agouti protein (ASIP), determining a lower activity of circulating MSH and of melanocortotropin receptors (MCRs) 1 and 4. MCR1 is fundamental in melanocyte DNA repair and melanogenesis, and a reduction of its activity could well account for the increased incidence of MM. All these changes are ultimately caused by the leptin resistance normally present on obese individuals, that is a low effectiveness of leptin in spite of its high circulating level.

Effect of Gan-Pi regulatory needling in treating chloasma

To study the effect of Gan-Pi regulatory needling (GPRN) in treating chloasma and its influences on female sex hormones, superoxide dismutase (SOD), lipid peroxide (LPO) and melanocyte-stimulating hormone (MSH). Ninety chloasma patients were equally randomized to three groups, the treatment group treated with GPRN, the control group treated with conventional Western medicine and the blank group untreated. Changes in the scores of skin lesion (area and color) and symptom, as well as blood levels of female sex hormones, MSH, SOD and LPO were observed and compared after 3 months of treatment. In the treatment group, the scores of skin lesion area and color were reduced from 2.76 + or - 0.96 and 2.48 + or - 0.78 before treatment to 1.42 + or - 0.42 and 1.03 + or - 0.41 after treatment, respectively, while in the control group they were from 2.78 + or - 1.06 and 2.53 + or - 0.88 to 1.58 + or - 1.23 and 1.28 + or - 0.96, respectively, all showing significant changes (P<0.05); the scores were insignificantly changed in the blank group (P>0.05). At the same time, the score of symptoms in the treatment group significantly improved after treatment (P<0.05), significantly different from that of the other two groups. Comparison of female sex hormones among groups showed no significant differences either before or after treatment. The level of LPO decreased and SOD increased in both the treatment group and the control group significantly (all P<0.05), but significant lowering of MSH was only seen in the treatment group (P<0.05). GPRN can effectively lessen the size and lighten the color of chloasma, improve the accompanying symptoms in patients and decrease LPO and MSH levels and increase the SOD level, but will not affect the level of the female sex hormones.

Plasma α–melanocyte-stimulating hormone: sex differences and correlations with obesity

Rodent experiments raise the possibility of a regulatory role of peripheral α–melanocyte-stimulating hormone ( α-MSH) in obesity and metabolism, but human data on peripheral α-MSH levels remain fragmentary. Because of the possible relationship between α-MSH and obesity, we endeavored to test the hypothesis that higher levels of α-MSH in obese patients would correlate with leptin levels and with other markers of obesity. Sixty normal-weight to obese healthy men and women participated. Weight, measures of body composition, and diet diaries were obtained; fasting blood was analyzed for α-MSH, lipids, glucose, insulin, leptin, and adiponectin. To begin to understand the source of peripherally measured hormones, α-MSH was also measured in serum samples from 5 individuals with untreated Addison disease. Levels of α-MSH were higher in men vs women (10.1 ± 4.3 vs 7.6 ± 3.4 pmol/L, P = .019), and α-MSH levels were higher in patients with Addison disease vs controls (17.7 ± 2.3 vs 8.7 ± 0.52 pmol/L, P < .001). Measures of adiposity correlated with insulin and leptin in men and women, and with adiponectin in women. α–Melanocyte-stimulating hormone levels did not correlate significantly with any parameter of adiposity or diet composition. The elevated α-MSH levels in patients with untreated Addison disease suggest possible pituitary secretion of α-MSH to the periphery. The lack of correlation between peripheral α-MSH and parameters of adiposity suggests that endogenous plasma α-MSH levels are not a metric for body composition per se.

Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanisms

Occupants of water-damaged buildings (WDBs) with evidence of microbial amplification often describe a syndrome involving multiple organ systems, commonly referred to as “sick building syndrome” (SBS), following chronic exposure to the indoor air. Studies have demonstrated that the indoor air of WDBs often contains a complex mixture of fungi, mycotoxins, bacteria, endotoxins, antigens, lipopolysaccharides, and biologically produced volatile compounds. A case-series study with medical assessments at five time points was conducted to characterize the syndrome after a double-blinded, placebo-controlled clinical trial conducted among a group of study participants investigated the efficacy of cholestyramine (CSM) therapy. The general hypothesis of the time series study was that chronic exposure to the indoor air of WDBs is associated with SBS. Consecutive clinical patients were screened for diagnosis of SBS using criteria of exposure potential, symptoms involving at least five organ systems, and the absence of confounding factors. Twenty-eight cases signed voluntary consent forms for participation in the time-series study and provided samples of microbial contaminants from water-damaged areas in the buildings they occupied. Twenty-six participants with a group-mean duration of illness of 11 months completed examinations at all five study time points. Thirteen of those participants also agreed to complete a double-blinded, placebo-controlled clinical trial. Data from Time Point 1 indicated a group-mean of 23 out of 37 symptoms evaluated; and visual contrast sensitivity (VCS), an indicator of neurological function, was abnormally low in all participants. Measurements of matrix metalloproteinase 9 (MMP9), leptin, alpha melanocyte stimulating hormone (MSH), vascular endothelial growth factor (VEGF), immunoglobulin E (IgE), and pulmonary function were abnormal in 22, 13, 25, 14, 1, and 7 participants, respectively. Following 2 weeks of CSM therapy to enhance toxin elimination rates, measurements at Time Point 2 indicated group-means of 4 symptoms with 65% improvement in VCS at mid-spatial frequency—both statistically significant improvements relative to Time Point 1. Moderate improvements were seen in MMP9, leptin, and VEGF serum levels. The improvements in health status were maintained at Time Point 3 following a 2-week period during which CSM therapy was suspended and the participants avoid re-exposure to the WDBs. Participants reoccupied the respective WDBs for 3 days without CSM therapy, and all participants reported relapse at Time Point 4. The group-mean number of symptoms increased from 4 at Time Point 2 to 15 and VCS at mid-spatial frequency declined by 42%, both statistically significant differences relative to Time Point 2. Statistically significant differences in the group-mean levels of MMP9 and leptin relative to Time Point 2 were also observed. CSM therapy was reinstated for 2 weeks prior to assessments at Time Point 5. Measurements at Time Point 5 indicated group-means of 3 symptoms and a 69% increase in VCS, both results statistically different from those at Time Points 1 and 4. Optically corrected Snellen Distance Equivalent visual acuity scores did not vary significantly over the course of the study. Group-mean levels of MMP9 and leptin showed statistically significant improvement at Time Point 5 relative to Time Points 1 and 4, and the proportion of participants with abnormal VEGF levels was significantly lower at Time Point 5 than at Time Point 1. The number of participants at Time Point 5 with abnormal levels of MMP9, leptin, VEGF, and pulmonary function were 10, 10, 9, and 7, respectively. The level of IgE was not re-measured because of the low incidence of abnormality at Time Point 1, and MSH was not re-measured because previously published data indicated a long time course for MSH improvement. The results from the time series study supported the general study hypothesis that exposure to the indoor air of WDBs is associated with SBS. High levels of MMP9 indicated that exposure to the complex mixture of substances in the indoor air of the WDBs triggered a pro-inflammatory cytokine response. A model describing modes of

A time-series study of sick building syndrome: chronic, biotoxin-associated illness from exposure to water-damaged buildings

The human health risk for chronic illnesses involving multiple body systems following inhalation exposure to the indoor environments of water-damaged buildings (WDBs) has remained poorly characterized and the subject of intense controversy. The current study assessed the hypothesis that exposure to the indoor environments of WDBs with visible microbial colonization was associated with illness. The study used a cross-sectional design with assessments at five time points, and the interventions of cholestyramine (CSM) therapy, exposure avoidance following therapy, and reexposure to the buildings after illness resolution. The methodological approach included oral administration of questionnaires, medical examinations, laboratory analyses, pulmonary function testing, and measurements of visual function. Of the 21 study volunteers, 19 completed assessment at each of the five time points. Data at Time Point 1 indicated multiple symptoms involving at least four organ systems in all study participants, a restrictive respiratory condition in four participants, and abnormally low visual contrast sensitivity (VCS) in 18 participants. Serum leptin levels were abnormally high and alpha melanocyte stimulating hormone (MSH) levels were abnormally low. Assessments at Time Point 2, following 2 weeks of CSM therapy, indicated a highly significant improvement in health status. Improvement was maintained at Time Point 3, which followed exposure avoidance without therapy. Reexposure to the WDBs resulted in illness reacquisition in all participants within 1 to 7 days. Following another round of CSM therapy, assessments at Time Point 5 indicated a highly significant improvement in health status. The group-mean number of symptoms decreased from 14.9±0.8 S.E.M. at Time Point 1 to 1.2±0.3 S.E.M., and the VCS deficit of approximately 50% at Time Point 1 was fully resolved. Leptin and MSH levels showed statistically significant improvement. The results indicated that CSM was an effective therapeutic agent, that VCS was a sensitive and specific indicator of neurologic function, and that illness involved systemic and hypothalamic processes. Although the results supported the general hypothesis that illness was associated with exposure to the WDBs, this conclusion was tempered by several study limitations. Exposure to specific agents was not demonstrated, study participants were not randomly selected, and double-blinding procedures were not used. Additional human and animal studies are needed to confirm this conclusion, investigate the role of complex mixtures of bacteria, fungi, mycotoxins, endotoxins, and antigens in illness causation, and characterize modes of action. Such data will improve the assessment of human health risk from chronic exposure to WDBs.

Leech immunocytes contain proopiomelanocortin: nitric oxide mediates hemolymph proopiomelanocortin processing.

This report establishes the presence of mammalian-like proopiomelanocotropic hormone (POMC), and six of its peptides, including adrenocorticotropic hormone (ACTH) and melanocyte-stimulating hormone (MSH), in the immune tissues of the leech Theromyzon tessulatum. The 25.4-kDa protein was purified by high pressure gel permeation chromatography, anti-ACTH-affinity column, and reverse-phase HPLC. Its characterization was performed by Edman degradation, enzymatic treatments, and electrospray mass spectrometry. Leech POMC exhibits considerable amino acid sequence similarity to mammalian POMC. Of the six peptides, three showed high sequence similarity to their vertebrate counterparts met-enkephalin, alpha-MSH, and ACTH: 100, 84.6, and 70%, respectively; whereas gamma-MSH, beta-endorphin, and gamma-lipotropin hormone exhibited only 45, 20, and 10% sequence identity, respectively. No dibasic amino acid residues were found at the C terminus of the gamma- and beta-MSH peptides. In contrast, the leech alpha-MSH was flanked at its C-terminal by the Gly-Arg-Lys amidation signal. ACTH and corticotropin-like intermediary pituitary peptide were also C-terminally flanked by dibasic amino acid residues. The coding region of leech POMC was obtained by reverse transcription-PCR using degenerated oligonucleotide primers. Circulating levels of ACTH and MSH were 10 and 1 fmol/microl hemolymph, respectively. Morphine, in a dose-dependent manner, increased the levels of both peptides threefold; this effect was blocked by naloxone treatment. Similar results were found with the anandamide. Leech ACTH was processed to MSH by the enzymes neutral endopeptidase (24.11) and angiotensin-converting enzyme. Leech alpha-MSH had the same activity as authentic alpha-MSH in two bioasssay systems. Taken together, the study demonstrates that POMC is present in invertebrates and its immunoregulatory actions have been conserved during evolution.

Low-dose intralesional interferon alfa for discoid lupus erythematosus

The hyperpigmentations that occur during pregnancy may result from hormonal changes, a greater population of melanocytes in affected areas or greater sensitivity of the melanocytes to hormonal stimulation.4 Melanocyte-stimulating hormone (MSH), estrogen, and progesterone have each been implicated as causes. However, if these pigmentary changes are classified into two groups based on abnormalities of either MSH or estrogen/progesterone levels, there are specific clinical findings associated with each of these abnormalities as well as an area of overlap. The formation of new lentigines and nevi or darkening and enlargement of preexisting lesions may also result from increased levels of MSH and estrogen/progesterone.4,5 Ellis and Wheeland4 showed that melanocytic nevi excised from pregnant women, women who had delivered within I month, and women who were taking oral contraceptives had increased estrogen and progesterone binding compared with control subjects. Journal of the American Academy of Dermatology

Melanocyte-Stimulating Hormone and Persistent Tardive Dyskinesia: A Hypothesis

An increased incidence of abnormal perioral movements has recently been reported in drug-naive pinealectomized rats with further accentuation of these movements following administration of haloperidol. Analysis of the temporal course of the development of the perioral dyskinetic movements revealed that the onset of these movements occurred within 4 days postoperatively and peaked at 3 weeks to plateau over the following 4-6 weeks. Increased pituitary Melanocyte-stimulating hormone (MSH) content has been reported in pinealectomized rats. Elevation of MSH content in the pinealectomized rats occurred within 3 days of surgery and was followed by normalization within 4 weeks. These findings suggest that compensatory mechanisms involving hypothalamic-pituitary MSH release must have been activated to induce normalization of pituitary MSH levels. Moreover, reduction of pituitary MSH levels may have coincided with attenuation in the severity of the perioral dyskinetic movements. It is possible that the development of tardive dyskinesia (TD) may in part be associated with increased brain and plasma MSH levels and that impaired hypothalamic-pituitary regulatory mechanisms of MSH release may be associated with persistent TD. The pineal gland may be implicated in this process as diminished melatonin secretion may be associated with disinhibition of MSH release. Thus, the above hypothesis complements and extends the recently presented "melatonin hypothesis" and suggests that research of pineal-hypothalamic interactions may be crucial to the further understanding of TD.

Expression of melanocyte stimulating hormone receptors correlates with mammalian pigmentation, and can be modulated by interferons

The relationship between melanogenesis and the expression of melanocyte stimulating hormone (MSH) receptors on the surface of melanocytes was examined using sublines generated from the melanotic JB/MS melanoma. JB/MS cells were propagated in long term culture to allow for phenotypic drift in their characteristics of differentiation, and then were cloned; the cloned cells ranged from well differentiated and pigmented to undifferentiated and amelanotic. Spontaneous and MSH-induced melanogenesis in these different lines was measured and correlated with the number of MSH receptors expressed. After 6 months of in vitro culture, the ability of the cells to respond to MSH was significantly reduced, as were the number of MSH receptors expressed; the cells had reduced pigmentation and were relatively undifferentiated histologically. Subsequently, clonally-derived pigmented cells were found to have numbers of surface MSH receptors (approximately 60,000 per cell) and levels of melanogenic activity similar to the original JB/MS cell line. However, an amelanotic clone had an even more dramatically reduced level of pigmentation which correlated with a further decrease in the expression of MSH receptors (less than 1,000 per cell) and the production of a potent melanogenic inhibitor. We also examined the responses of these various sublines to alpha, beta, and gamma-interferons and found significant heterogeneity in their abilities to respond to these cytokines. This study clearly shows that there is a direct correlation between melanogenesis and the expression of MSH receptors on the surface of melanocytes, and that melanogenic inhibitors may be critically involved in the regulation of mammalian pigmentation.

Hormonal induction of kidney tumours in male hamsters. Inhibition of growth by a phenothiazine derivative (perphenazine)

Experiments have shown that long-term treatment of male hamsters with oestrogen will cause renal carcinomas, neoplastic changes in the pars intermedia of the pituitary and highly elevated levels of melanocyte-stimulating hormone (MSH). To test if MSH was fundamentally involved in renal carcinogenesis, a group of hamsters was treated for 317 days with perphenazine which is known to elevate MSH levels. A second group was treated with oestrogen while a third received a combination of oestrogen and perphenazine for a similar period of time. Serum MSH levels were significantly elevated in the perphenazine group but kidney tumours were absent. All oestrogen-treated animals developed kidney tumours but only 19% of those given the combined treatment developed kidney tumours despite highly elevated levels of MSH. The findings suggest that MSH does not play a significant role in renal carcinogenesis in the hamster. Perphenazine may inhibit the induction of oestrogen-induced tumours by competing with oestrogen for receptors in the kidney or may protect cells from toxic injury by stabilising cell and microsomal membranes. The phenothiazines are known to induce, and increase the activity of, microsomal enzymes and that may lead to enhanced detoxification of the carcinogen. Other effects of phenothiazines include elevation of prolactin levels. The fact that the body weight of animals treated with DES and perphenazine was significantly lower than that of the other groups may indicate that the reduction in tumour incidence was the result of a certain degree of undernutrition. Further work is required to elucidate the mechanism of tumour inhibition by phenothiazine derivatives.

Serum Melanocyte-Stimulating Hormone Levels and Pituitary Melanocyte-Stimulating Hormone Content during Pseudopregnancy in the Rat*

Pseudopregnancy (PSP) was induced in rats by vaginal stimulation and the levels of MSH in serum and pituitary were examined. One hour after vaginal stimulation, the serum MSH level was increased, and a cyclical variation was observed by the second day of PSP. There were two surges of about 50 pg/ml, one in the morning and the other at night. On the sixth day of PSP, the pattern of serum levels still showed two peaks, but while the nocturnal peak remained at 50 pg/ml, the diurnal value was halved. The pituitary MSH content also underwent cyclical variations; the lowest levels coincided with the peak levels in serum. These observations raise the possibility that MSH is involved in PSP.

The pars intermedia and renal carcinogenesis in hamsters

Male hamsters, 3 months of age, were treated for 9 months by thrice weekly injections of diethylstilboestrol (DES). All animals developed kidney tumours and histopathological examination showed that the intermediate lobes of the pituitary were hyperplastic and neoplastic. The content of melanocyte-stimulating hormone (MSH) in the pituitary glands of 17 control and 12 DES-treated animals was measured by bioassay and radioimmunoassay. Whan compared with control pituitaries, the concentration of immunoreactive a-MSH in treated animals was significantly elevated ( P < 0·005) with significant positive correlation between pituitary weight and total a-MSH content. The levels of bioactive MSH were also raised. Serum levels of immunoreactive a-MSH were consistently higher in treated animals. The possibility exists that the induction of kidney tumours by oestrogens in the male hamster is mediated via the pituitary gland and that MSH may be of significance in the process of carcinogenesis.

Stereological analysis of the effects of 6-hydroxydopamine on the ultrastructure of the melanocyte-stimulating hormone cell of the pars intermedia of the pituitary of Xenopus laevis

It has been confirmed that intracisternal administration of the sympatholytic compound 6-hydroxydopamine (6-OHDA) to the toad Xenopus brings about degenerative changes in the appearance of the catecholaminergic innervation of the pars intermedia of the pituitary. This observation has been extended by stereological analysis of the ultrastructural composition of the presumed melanocyte-stimulating hormone (MSH) cells of the pars intermedia, which reveals that following the administration of this compound there is an increase in the amount of rough endoplasmic reticulum and a decrease in the numbers of secretory granules. These changes are consistent with increased secretory activity and are considered to reflect the removal of an inhibitory catecholaminergic influence from the MSH cells. 6-OHDA also brings about a prolonged darkening of the animals, but it is suggested that this cannot be due entirely to increased circulating levels of MSH in view of the finding that 6-OHDA has a pituitary-independent effect on pigmentation, as demonstrated by the administration of 6-OHDA to hypophysectomised animals when a transitory darkening occurs.

A diurnal rhythm in melanocyte-stimulating hormone content of the rat pituitary gland and its independence from the pineal gland.

Resting pituitary melanocyte-stimulating hormone (MSH) content was studied in adult rats kept under a controlled 14 h light-10 h dark regimen. A diurnal rhythm was found in pituitary MSH levels, showing peak values at 4.00-6.00 p.m., and low values during darkness and the beginning of the light period. The normally occurring fall in pituitary MSH content between 6.00 p.m. and midnight was also found in rats exposed to a prolonged photoperiod. Sympathetic denervation of the pineal gland by superior cervical ganglionectomy, as well as pinealectomy, did not block the rhythm in pituitary MSH, and had no effect on pituitary MSH content. In addition, melatonin administered i.v. did not affect pituitary MSH levels, either when MSH activity was tested on the Anolis skin in vitro, or when the in vivo assay with hypophysectomized frogs (Rana pipiens) was used. It was concluded that the diurnal rhythm in pituitary MSH content is not directly related to the light-dark cycle and is not controlled by pineal melatonin or any otherpineal factor.

Plasma and pituitary MSH levels in the rat after lesions of the hypothalamus.

The long-term effect of hypothalamic lesions onplasma and pituitary levels of melanocyte-stimulating hormone (MSH) was examined in male rats. Lesions of the paraventricular nuclei (PVN) produced a large increase in both plasma and pituitary MSH levels, whereas lesions of the supra-optic nuclei had little effect. These results support the idea that MSH secretion is under an inhibitory control by the hypothalamus and suggest that the PVN are involved. The PVN may be involved in the release or production of an MSH release inhibiting factor (MIF), although the present results do not exclude the possibility that the PVN control MSH secretion through a direct innervation of the pars intermedia.

MSH Activity in Plasma and Pituitaries of Rats with Large Hypothalamic Lesions

The effect of medial basal hypothalamic lesions on plasma and pituitary melanocyte-stimulating hormone (MSH) was determined in albino rats. 32 days postoperatively, plasma levels of MSH were elevated