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Results for “Pro-Opiomelanocortin”

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Expression of mouse proopiomelanocortin in an insulinoma cell line. Requirements for beta-endorphin processing.

Proopiomelanocortin (POMC) is a neuroendocrine precursor protein which is processed at paired basic amino acids in a tissue-specific manner. To study this phenomenon, a vaccinia virus recombinant, which directs the synthesis of mouse POMC (VV:mPOMC) was constructed and used to infect epithelial (BSC-40) and endocrine (Rin m5F) cell lines. Bona fide mPOMC was produced in both cell types and beta-endorphin immunoreactivity was secreted in a nonregulated manner from BSC-40 cells and in a regulated manner from Rin m5F cells. Although the precursor was not cleaved to smaller beta-MSH or beta-endorphin immunoreactive peptides in BSC-40 cell extracts, Rin m5F cells produced primarily authentic gamma-lipotropin and des-acetyl beta-endorphin. Furthermore, production of these peptides was restricted to the regulated secretory pathway in Rin m5F cells. Site-directed mutagenesis was then used to change the inefficiently recognized Lys-Lys potential cleavage site near the carboxyl terminus of beta-endorphin to Lys-Arg. Expression of the mutant precursor in Rin m5F cells resulted in the synthesis of both des-acetyl beta-endorphin and beta-endorphin.

Adenoma, Islet Cell↗

Corticotropin-releasing factor and vasopressin production in the rat pituitary tumor 7315a: biochemical and immunohistochemical studies.

In order to investigate the production and secretion of hypothalamic factors by the prolactin and proopiomelanocortin (POMC)-derived, peptide-producing, transplantable rat pituitary tumor 7315a, we determined the concentrations of corticotropin-releasing factor (CRF)- and vasopressin (AVP)-like immunoreactivities (IR) in the tumor extracts [14.0 +/- 1.6 (SE) and 4.2 +/- 0.9 pmol/g, respectively] and incubation media (0.26 +/- 0.01 and 0.07 +/- 0.01 pmol/10(7) cells/h, respectively). Total peptide content correlated well with tumor weight. Moreover, there is a very good correlation between the CRF and AVP IR, but not as good between CRF or AVP IR and POMC peptide IR tumor contents. Tumor extracts were chromatographed on Sephadex G-75 and compared with chromatograms of stalk median eminence (SME) extracts from normal Buffalo rats. CRF IR in tumor chromatograms gave an unusual pattern of peaks. About 31% of the total CRF IR was eluted in the high molecular weight region. The major portion of CRF IR was located in a wide region of lower molecular weight. The AVP radioimmunoassay revealed a similar pattern of peaks in tumor and SME chromatograms. A propressophysin-like peak and a smaller peak coeluting with synthetic AVP were detected. Immunohistochemical staining of consecutive sections of the tumor indicated that AVP and CRF are often found in the same cell, but the CRF and AVP-producing cells are clearly distinct from the POMC peptide-producing cells.

Adrenocorticotropic Hormone↗

[Gonadal opioids and testicular function].

A review is presented on the occurrence of opioid systems within mammalian testes at different stages of sexual development. Identification of the messenger ribonucleic acid sequences (mRNA) related to the three opioid precursor families and as well as characterization and localization of their main derivates may account for the importance of such systems within reproductive tissues. These data are supported by experimental in vivo and in vitro studies giving evidence that opioid peptides are produced locally and may exert paracrine and/or autocrine effects within the testes.

Animals↗

[Evaluation of various parameters in the differential diagnosis of Cushing's disease and Cushing's syndrome caused by adrenal adenoma].

Evaluation of the clinical and biochemical parameters for differential diagnosis of two types of Cushing's syndrome, pituitary-dependent Cushing's disease and adrenal adenoma, was studied with analysis of the histories of 79 cases of Cushing's disease and 23 cases of adrenal adenoma. The data show that the symptoms, signs and the routine biochemical analyses were not significantly different between two groups. High-dose dexamethasone suppression test had about 90% coincidence rate in the differential diagnosis with 24-hour urine free cortisol (UFC), which was better than 24-hour urine 17-OHCS. Interestingly, low-dose dexamethasone test was highly valuable and the 24-hour urine 17-KS quite helpful in the differential diagnosis of two types of Cushing's syndrome. Serum N-POMC measurement was the most valuable among the parameters, because there was no overlap between the two groups of Cushing's syndrome.

17-Ketosteroids↗

[ACTH-secreting tumors. Deregulation of the proopiomelanocortin gene and alterations in processing].

ACTH is produced by proteolysis of a polypeptide precursor, proopiomelanocortin (or POMC). Various POMC-derived peptides are cosecreted with ACTH. Analysis of the ACTH--and its "satellite" peptides--molecular forms establishes the POMC "maturation profile" in different tissues. This profile is identical in normal and tumoral pituitaries (Cushing's disease and/or Nelson's syndrome). It is often altered in non-pituitary tumors responsible for the ectopic ACTH syndrome: abnormal peptides may be generated (CLIP h beta MSH5-22) which can be detected in blood. Analysis of POMC gene transcription in pituitary tumors shows no abnormality. In some non-pituitary tumors the activation of upstream promoters up to 369 nucleotides from the normal (pituitary) transcription initiation site can be shown. In normal non-pituitary tissues a third type of transcription is observed generating a short and probably non-functional messenger RNA limited to a portion of the gene non-coding region.

Adrenal Gland Neoplasms↗

Increased pro-opiomelanocortin-derived peptide release in myotonic dystrophy.

The response of plasma immunoreactive (IR)-ACTH, IR-beta-endorphin (beta-END) and IR-cortisol to insulin-induced hypoglycaemia, an acute stimulus to the pituitary corticotrophs through the central nervous system, and to synthetic ovine corticotrophin-releasing hormone (CRH), a direct corticotroph stimulator, were studied in normal males and males with myotonic dystrophy. Myotonics had an increased IR-ACTH and IR-beta-END response to hypoglycaemia and an increased IR-ACTH response to CRH compared with normals. Plasma IR-cortisol response were not different in either group of subjects to both stimuli. This neuroendocrine abnormality in myotonic dystrophy may represent a manifestation of the purported specific cell membrane defect underlying the disease. This is the first report of an abnormality in proopiomelanocortin peptide release in myotonic dystrophy.

Adolescent↗

Influence of age on neurotransmitter function.

Regulation by neurotransmitters of anterior pituitary hormone secretion is complex and a thorough understanding of their normal role in hormone secretion is a prerequisite to understanding their involvement in age-related changes in endocrine function. To date, uncertainties far out-number demonstrated causative relationships between alterations in neurotransmitter release and resulting age-associated changes in hormone secretion. The best demonstrated relationships are the following. First, a decline in function of the TIDA system is responsible, in part, for the age-related elevation in prolactin secretion and may be involved in the decline in LH secretion. Second, the age-related decrease in hypothalamic norepinephrine turnover plays a role in the decline in LH and GH secretion and may be involved in alterations in TSH secretion during aging. Third, the decline in circadian activity of suprachiasmatic nucleus serotoninergic neurons may account for the blunting of circadian rhythms in the secretions of several anterior pituitary hormones in old animals. Fourth, evidence exists for an age-related decline in function of LHRH neurons, which may contribute to the observation of blunted LH secretion in old animals. Finally, somatostatin release may be increased in old animals, which likely contributes to the age-related decline in GH secretion. Other hypothalamic-releasing hormones have only recently been isolated and characterized; thus, little research on their age-related alterations has been done. Research on these neuropeptides will contribute further to our understanding of the role of neurotransmitters in age-related alterations in hormone secretion.

Aging↗