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)

We report on a patient with ACTH and FSH producing invasive pituitary adenoma complaining of cutaneous pigmentation. Elevations in plasma ACTH, beta-endorphin and cortisol levels as well as urinary 17-OHCS and cortisol excretion were found. Serum FSH concentration was just within the upper limit of the normal range, whereas serum LH level was reduced and alpha-subunit level was normal. Roentogenographic examination showed an almost complete loss of sellar floor and destruction of the posterior clinoids and dorsum sella. CT scan and MRI demonstrated an enlarged tumor invasion of the clivus and its extension to the sphenoid sinus. After subtotal removal of the large pituitary tumor, serum cortisol and plasma beta-endorphin levels as well as plasma ACTH concentrations returned to normal and serum FSH levels also remarkably decreased. Histologically, the tumor corresponded to a chromophobe, slightly PAS positive adenoma. These tumor cells exhibited positive immunostaining with antibody to ACTH (1-24), beta-LPH, beta-endorphin and FSH, while immunostaining of the adenoma cells was negative for LH, TSH, GH and prolactin. The immunogold technique also demonstrated ACTH and FSH particles in the secretory granules in the cytoplasm of the adenoma cells. Some of the tumor cells disclosed Crooke's hyalinization and type I microfilament occupied most of the cytoplasm. In the present study, a very rare case of ACTH and FSH producing invasive pituitary adenoma is reported.
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PMID:An ACTH and FSH producing invasive pituitary adenoma with Crooke's hyalinization. 171 63

A 58-year-old woman was admitted to our hospital with complaints of general fatigue, thirst and lumbago. A diagnosis of Cushing's syndrome was made on the basis of elevated serum levels of cortisol and adrenocorticotropic hormone (ACTH). Although Cushing's disease was most suspected, no evident image of pituitary adenoma could be found on brain CT scan and MRI. Therefore, treatment with oral Trilostane was started. Three months after admission, left hemiplegia was noticed and cerebral abscess in the right frontal lobe was demonstrated by brain CT scan. In spite of surgical removal of the abscess by total resection, she had a relapse in the same site and also developed a new lesion in the left lateral lobe. Surgical drainage was performed and Nocardia asteroides was isolated from the drained pus. An intensive chemotherapy with aminobenzylpenicillin (ABPC) and latamoxef (LMOX) in combination resulted in marked decrease in size of the lesion in the brain and subsequent improvement of left hemiplegia was achieved. Since approximately one month before when a diagnosis of cerebral abscess was made, there had been demonstrated a coin lesion in the right middle field on chest X-ray films. This lesion in the right lung disappeared concomitantly with the improvement of the lesions in the brain. This fact strongly suggests that the lesion in both brain and lung were of the same nature. Nocardia is known to make a primary lesion in the lung after being inhaled and then through hematogenous dissemination to make distant lesions in various sites, especially in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of Cushing's syndrome associated with Nocardia cerebral abscess]. 206 9

The molecular forms of ACTH secreted by established human small cell lung cancer (SCLC) cells and primary cultures derived from a bronchial carcinoid tumour, a pituitary adenoma and hyperplastic pituitary tissue have been characterized by Sephadex G-75 chromatography and quantified with two novel immunoradiometric assays for ACTH and ACTH precursor peptides. Pro-opiomelanocortin (POMC; Mr 31,000) and pro-ACTH (Mr 22,000) were secreted by all cell types. No smaller peptides were identified in the culture media from SCLC and bronchial carcinoid cells, implying a deficiency in the enzymes and/or intracellular organelles required for extensive POMC processing. A more heterogeneous profile of ACTH-containing peptides was produced by cells of pituitary origin, indicating more extensive proteolytic processing of POMC. However, the major peptide secreted by cells from a large aggressive pituitary adenoma was unprocessed POMC (Mr 31,000). These results suggest that both lung and pituitary cells in vitro retain their in-vivo pattern of POMC processing and provide valuable models in which to study the regulation of ACTH synthesis and secretion.
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PMID:Comparison of ACTH and ACTH precursor peptides secreted by human pituitary and lung tumour cells in vitro. 215 69

A 49-year old woman with a 5-year history of Cushing's syndrome was evaluated. Biochemical measurements revealed high cortisol and adrenocorticotropic hormone (ACTH) levels consistent with the ACTH-dependent type of Cushing's syndrome. However, the source of ACTH seemed to be autonomous as she demonstrated abnormal feedback control, with lack of response to metyrapone and high coses of dexamethasone. A search for an ectopic ACTH-secreting nonpituitary neoplasm was unsuccessful. Transsphenoidal pituitary exploration revealed a normal pituitary gland, but an ectopic pituitary adenoma was found incidentally in the mucosa of the sphenoid sinus. This adenoma stained strongly positive for ACTH on immunocytochemical studies. Resection of this lesion led to remission of the Cushing's syndrome. This variant of ACTH-dependent Cushing's syndrome can mimic the ectopic ACTH-dependent type and should be looked for in patients who fail to respond to pituitary operation.
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PMID:Cushing's syndrome caused by an ectopic pituitary adenoma. 282 48

Computed tomographic (CT) scans of the adrenal glands were obtained in nine patients with Cushing disease as a result of an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma and macronodular hyperplasia of the adrenal glands. The findings were compared retrospectively with those in six patients with Cushing syndrome as a result of an autonomous adrenal adenoma and 16 with Cushing syndrome as a result of ectopic ACTH production. Seven of nine patients with macronodular adrenal hyperplasia had hyperplastic adrenal glands in addition to single or multiple focal adrenal nodules. The six patients with hypercortisolism caused by an autonomous adrenal adenoma showed atrophic (four patients) or normal (two patients) ipsilateral and contralateral adrenal glands. Fourteen of 16 patients with the ectopic ACTH syndrome had hyperplasia of the adrenal glands without nodularity, and only two had focal nodules.
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PMID:Macronodular adrenal hyperplasia in Cushing disease. 282 31

Ketoconazole has been used as a palliative treatment of Cushing's syndrome, due to its ability to lower cortisol production. We evaluated the effects of ovine Corticotropin Releasing Hormone (oCRH) 100 micrograms i.v. on ACTH and cortisol levels in 6 patients with Cushing's disease before and after treatment with ketoconazole 600 mg/day. Both hormones increased after oCRH. During ketoconazole, cortisol was lowered to normal levels and its response to oCRH was impaired. After treatment, basal ACTH showed variable changes while the response to oCRH was markedly enhanced compared to that before ketoconazole. In vitro: In a continuous perfusion system of isolated anterior pituitary cells from rats or human anterior pituitary adenoma, producing ACTH, ketoconazole 10(-5)-10(-6) M showed no inhibitory effects on both basal or lisine-vasopressin and oCRH stimulated ACTH secretion. Our findings confirm the inhibitory action of ketoconazole on basal and stimulated cortisol secretion. No inhibition of ACTH levels was observed both in vivo and in vitro.
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PMID:ACTH response to corticotropin releasing hormone in Cushing's disease before and after ketoconazole: in vivo and in vitro studies. 283 92

The effects of corticotropin-releasing hormone (CRH) and dexamethasone on proopiomelanocortin (POMC) mRNA levels in cultured pituitary adenoma cells were studied in 10 patients with Cushing's disease. As a control, POMC mRNA levels in cells from nonadenomatous tissues were examined in four patients. Human POMC mRNA in the cells was analyzed by Northern blot hybridization. Human POMC DNA probe hybridized with only a single size class of RNA (approximately 1,200 nucleotides) from the adenoma and nonadenoma cells of each patient. The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone. CRH increased POMC mRNA levels in these cells in a dose- and time-dependent manner. The minimum concentration of CRH required to elevate POMC mRNA levels in these cells exposed for 15 h was 0.1 nM. The minimum duration of 1 nM CRH treatment required to increase these levels was 3 h under our conditions. Inhibitory effects of 1 and 10 micrograms/dl dexamethasone on ACTH release and POMC mRNA levels in nonadenoma cells were greater than those in adenoma cells. These results suggest the following: (a) that the mRNA in cultured pituitary adenoma cells is qualitatively the same as that in vivo; (b) that responses of mRNA levels to CRH are time- and dose-dependent; and (c) that adenoma cells resist the inhibitory effect of dexamethasone on POMC mRNA levels and ACTH release.
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PMID:Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro. 283 42

Arginine vasopressin (AVP) is a potent secretagogue for adrenocorticotropin (ACTH) release from normal corticotropes and from ACTH-secreting pituitary adenoma cells. To explore the mechanism underlying this action, we investigated the effects of AVP on Ca2+-dependent action potentials and Ca2+ currents in cultured human ACTH-containing pituitary tumor cells (hACTH adenoma cells). Pituitary adenoma fragments removed at surgery from two patients with Cushing's disease were dispersed, and the isolated cells were grown in monolayer culture. Most of the cells showed ACTH immunoreactivity that persisted even after as much as 2 months in culture. Current clamp and voltage clamp recordings were carried out using the patch-clamp technique in the whole cell configuration. AVP produced an increase in the amplitude and duration of action potentials in these cells, and substantially enhanced the transient after-hyperpolarization after each spike. Under voltage the transient after-hyperpolarization after each spike. Under voltage clamp, hACTH adenoma cells showed two Ca2+ current components: a low-threshold, rapidly inactivating (T-type) current; and a higher threshold, slowly inactivating (L-type) current. AVP markedly increased the amplitude of the L-type current without affecting the T-type current. These data suggest that AVP may enhance Ca2+ entry associated with action potentials by potentiating the activity of L-type Ca2+ channels. The resulting rise in cytosolic free Ca2+ may be a key link in the process by which AVP stimulates ACTH release in the pituitary.
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PMID:Vasopressin enhances a calcium current in human ACTH-secreting pituitary adenoma cells. 284 18

In an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.
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PMID:Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. 285 94

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81


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