Human beta-melanocyte-stimulating hormone revisited.

Abstract

It is generally accepted that human 13-melanocyte-stimulating hormone (h.BMSH) does not normally exist in humans but was merely an artifactually generated 22-amino acid peptide corresponding to a lipotropin (LPH) fragment (residues 35-56). We examined whether the shorter 18-amino acid peptide hBMSH-(5-22) could be detected in some human tissues. MATERIALS AND METHODSTissue Collection. The following tumors were surgically obtained from five patients with ectopic ACTH syndrome: tumors E1-E4 were bronchial carcinoid tumors; tumor E5 was a thymic carcinoid tumor. Fragments of pituitary corticotropic adenomas from two patients with Nelson syndrome (N1, N2) were surgically obtained by the transsphenoidal approach. In all cases, macroscopically homogeneous tumor fragments with no evidence of local necrosis were quickly selected by the surgeon, immediately frozen in liquid nitrogen, and subsequently stored at -85°C. Two normal human pituitaries (P1, P2) and hypothalami (HT1, HT2) were obtained at autopsy 2-and 6-hr post-mortem from patients with no evidence of endocrine disease and no history of prior hormonal treatment. They were frozen and stored as indicated. Patients with ACTH-producing tumors had not been subjected to either radiotherapy or chemotherapy.Tissue Extraction. Tissue fragments were homogenized in ice-cold 5 M acetic acid (10 ml/g of tissue) containing 1 mM phenylmethylsulfonyl fluoride, by three to five 15-sec bursts in a PCU2 Polytron (Polytron, Elkhart, IN). The homogenates were centrifuged at 5000 x g for 30 min at 4°C, and the supernatants were lyophilized in multiple aliquots that were subsequently used for RIA and/or chromatographic studies.

Pituitary-like proopiomelanocortin transcripts in human Leydig cell tumors.

“…These studies also revealed two unexpected findings: (a) the testis POMC RNA is shorter than the pituitary POMC mRNA, being -800 nt long (25,26). We (38). Contrary to the previous RIA, h(3LPH and hI3MSH showed 100% cross-reactivity, and hflMSH5-22 had no cross-reactivity.…”

Mutational Analysis of the Pro-opiomelanocortin Gene in French Obese Children Led to the Identification of a Novel Deleterious Heterozygous Mutation Located in the α-Melanocyte Stimulating Hormone Domain

“…Our findings provide additional support for a more critical role of ␤MSH than of ␣MSH in the control of human energy balance (12,17,18). Because ␤MSH is present in the human hypothalamus (25) and seems to have higher affinity for the hMC4R (26), it is likely to be the more physiologically relevant endogenous ligand for the hMC4R (when compared with ␣MSH). The obese phenotype associated with the POMC M, male, F, female; age at obesity onset is defined as age with BMI above the 97th percentile; Ins T0, fasting insulinemia; Gly T0: fasting glucose; HOMA, homeostasis model assessment index defined as (fasting insulin level ϫ fasting glucose level) divided by 22.5; TG, triacylglycerol; Chol, total cholesterol; ?, data not available; ND, not determined.…”

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

“…Subsequently, the peptide was considered to be an artifact of procedure and did not exist in humans. However, more recently, naturally occurring ␤-MSH-octadecapeptide has been identified in human hypothalamus (Bertagna et al, 1986). The peptide corresponds with the ␥-LPH (41-58) sequence.…”