Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gonadotropin-releasing hormone (GnRH) is a key hypothalamic peptide that controls the secretion of pituitary gonadotropins, particularly luteinizing hormone (LH), and hence gonadal function. Hypothalamic GnRH is released in a pulsatile manner. In the female, the pattern of GnRH pulses, i.e., pulse frequency and amplitude, varies during different reproductive stages and among different species. Several central and peripheral signals modulate GnRH neuronal activities. Some of these signals are stimulatory to GnRH release, e.g., norepinephrine (NE) and neuropeptide Y (NPY); some are inhibitory, e.g., beta-endorphin and interleukin-1; others are both stimulatory and inhibitory, e.g., estradiol-17 beta (E2). The neuronal structures and chemical interactions that result in pulsatile GnRH release remain unresolved. However, the core of the so-called 'GnRH pulse-generator' likely involves NE and NE transporter (NET, the protein for pre-synaptic re-uptake of NE). Both secretion and re-uptake of NE may determine hypothalamic NE availability. Many of the GnRH-stimulating and GnRH-inhibiting signals may influence the 'pulse-generator' by acting on GnRH neurons as second level signals. Hypothalamic GnRH is also released in a "surge" manner that is triggered either by increasing levels of circulating steroids (E2 and progesterone) during the preovulatory period in spontaneous-ovulating species, or by coitus in induced-ovulating animals. The sequential steps and mechanisms by which the GnRH surge occurs after E2 or coitus are not clear. However, it is unlikely that the E2 or coital stimuli act directly on GnRH neurons; E2 receptors have not been found in GnRH cells whereas coital signals must stop in the brainstem before they reach the hypothalamus. The brainstem may be an extra-hypothalamic site where both E2 and coital stimuli are transformed into GnRH-stimulating signals. One such signal may be NE whose brainstem cell bodies send terminals into the hypothalamus. Evidence from our laboratory suggests that a hypothalamic NE surge occurs at the time of the preovulatory GnRH surge in both the monkey and rabbit. Moreover, gene expression of both tyrosine hydroxylase (the rate-limiting enzyme for NE synthesis) and NET (the rate-limiting factor for synaptic NE transmission) in the brainstem increases after E2 in the monkey and after coitus in the rabbit. Other hypothalamic and/or brainstem signals, i.e., NPY, galanin, beta-endorphin, nitrous oxide and gamma aminobutyric acid, are likely involved in generating, maintaining and/or modulating the GnRH surge process. A better understanding of the up-stream GnRH-regulating signals will help improve treatments for many reproductive disorders associated with stress, obesity, infection and aging.
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PMID:Neuroendocrine signals in the regulation of gonadotropin-releasing hormone secretion. 955 Dec 47

Ectopic adrenocorticotropic hormone (ACTH) production by the pancreatic neuroendocrine tumor (p-NET) is relatively rare, and patients with this tumor show poor prognosis. In this study, we present the case of a 64-year-old woman who presented with ectopic ACTH syndrome due to p-NET with multiple liver metastases. Computed tomography revealed that she had multiple masses in the liver and a solid mass in the head of the pancreas. Endocrinological examinations revealed markedly elevated plasma ACTH (735.0 pg/mL) and cortisol (34.7 microg/dL) levels associated with hypokalemia (2.7 mEq/L), diabetes and typical Cushingoid features. Histological examinations by needle biopsy of liver tumors in S5 and S8 indicated metastatic ACTH-producing NET, which was also confirmed by venous sampling. The metastatic live tumor was somatostatin receptor (SSTR)-2a- and SSTR-5-positive as revealed by immunohistochemical staining, and reverse transcription polymerase chain reaction revealed divergent expression patterns of SSTRs, pro-opiomelanocortin, and gastrin mRNA. To avoid complications of hypercortisolemia, metyrapone was first administered to reduce the cortisol levels. After near-normalization of cortisol levels, transarterial chemoembolization and somatostatin analogue treatment were performed. The combination of these treatments effectively decreased ACTH and cortisol levels and also ameliorated hyperglycemia. We have achieved controlled hormone secretion and prevented tumor growth in this patient for more than 20 months, suggesting that highly individualized treatment for NET should be undertaken because of its divergent and heterogeneous characteristics.
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PMID:A case of ectopic adrenocorticotropic hormone-producing pancreatic neuroendocrine tumor with multiple liver metastases. 2003 67

Pancreatic neuroendocrine tumors (p-NETs) entail a vast array of tumors, which can vary from benign neoplastic growths to rapidly aggressive malignancies. Such is the case with ectopic adrenocorticotropic hormone (ACTH)-producing p-NETs. These tumors have been found to be quite aggressive and a challenge to treat, especially due to the occurrence of metastatic disease even after resection of the primary tumor. We discuss the case of a 44-year-old female who initially presented with vague, non-specific symptoms, in which a malignant p-NET was found to be the cause of her clinical presentation. Although resection of the pancreatic mass was performed, the patient presented again with metastatic disease to the liver.
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PMID:Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production: a case report and review of literature. 2402 41

Cushing's syndrome caused by an ectopic tumour secreting adrenocorticotropic hormone (ACTH) is not common. Furthermore, an ACTH-secreting panreatic neoplasm is extremely rare. We present a 27-year old female patient suffering from a pancreatic neuroendocrine tumour (p-NET) with extensive pelvic metastases, which could secrete ACTH and cause Cushing's syndrome. The postoperative pathologic examinations of this patient prompted pancreatic poorly differentiated neuroendocrine tumour with extensive metastases of bilateral ovarian, uterus and pelvic peritoneum. The immunohistochemical staining of her tumour tissues was positive for Chromogranin A, Synaptophysin and ACTH. The main aim of this article is to share the experience of her diagnosis and treatment and to review the relevant literature, with an emphasis on discussing the possible transfer modes. Moreover, we strongly suggest that a careful examination of pelvic cavity during the follow-up of patients diagnosed as ACTH-secreting p-NET should also be carried out.
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PMID:Cushing Syndrome Caused by a Pancreatic Neuroendocrine Tumour and Its Pelvic Metastases. 2835 55