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)

To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome.
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PMID:Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro. 825 33

Cushing's disease resulting from intrasellar corticotropin-releasing hormone (CRH)-secreting gangliocytomas is very rare, and only two such cases have been reported in the literature to date. The authors present a third case in which an adrenocorticotropic hormone-secreting pituitary adenoma was found in addition to a gangliocytoma in a 10-year-old girl with clinical and endocrinological symptoms of Cushing's disease. Computed tomographic and magnetic resonance imaging scans showed a suprasellar and parasellar tumor. A green-colored, heterogeneous tumor and a small adenoma were removed transsphenoidally. Histological examination revealed a large gangliocytoma immunoreactive for CRH and a small, mucoid cell pituitary adenoma immunoreactive for ACTH. This is the first case of such a tumor causing Cushing's disease in a child. It might exemplify induction of an ACTH-secreting pituitary adenoma by means of chronic overstimulation of CRH.
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PMID:Cushing's disease in a child caused by a corticotropin-releasing hormone-secreting intrasellar gangliocytoma associated with an adrenocorticotropic hormone-secreting pituitary adenoma. 826 95

We sought to enhance the sensitivity of selective bilateral blood sampling to determine adrenocorticotropin (ACTH) and prolactin levels in the inferior petrosal sinus (IPS) by administering two stimulatory agents--corticotropin-releasing factor (CRF) and thyrotropin-releasing hormone (TRH). We then determined the ACTH and prolactin levels in the IPS of 10 patients with Cushing's disease. After peripheral administration of both CRF and TRH, ACTH levels were significantly higher on the tumor side in all patients. The prolactin level was significantly higher on the tumor side when CRF or TRH was used to stimulate pituitary secretion. Postsurgical immunohistochemistry studies revealed production of both ACTH and prolactin in tumor cells, explaining the abnormal secretion pattern of the pituitary adenoma. The use of CRF and TRH may therefore improve the reliability of selective blood sampling and tests from the IPS in those cases of Cushing's disease for which noninvasive methods have otherwise failed to clarify the diagnosis.
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PMID:Selective bilateral blood sampling from the inferior petrosal sinus in Cushing's disease: effects of corticotropin-releasing factor and thyrotropin-releasing hormone on pituitary secretion. 826 24

We examined the effect of phorbol ester on growth hormone (GH)-releasing hormone (GRH)-induced GH secretion and cyclic adenosine monophosphate (cAMP) production in three pituitary adenomas and thyrotropin-releasing hormone (TRH)- and corticotropin-releasing hormone (CRH)-induced redistribution of protein kinase C (PKC) from cytosol to membrane in a pituitary adenoma resected from patients with acromegaly. GRH stimulated GH secretion in accordance with cAMP production in three cases, whereas 12-O-tetradecanoyl phorbol-13 acetate (TPA) stimulated GH secretion with cAMP production in one case. Simultaneous addition of GRH and TPA enhanced cAMP production in three pituitary adenomas. Moreover, addition of TPA with GRH resulted in additive secretion of GH in vitro. In one case, we were able to measure PKC activity and prove translocation of PKC stimulated by TRH and CRH in accordance with GH secretion in vitro and in vivo. These results suggest that TPA, an activator of PKC, has a stimulatory effect on GRH-induced cAMP production and that, finally, TRH- and CRH-induced PKC activation may cause greater secretion of GH by enhancement of cAMP production in human GH-hypersecreting adenoma cells.
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PMID:Growth hormone secretion in human acromegalic pituitary adenomas: cyclic adenosine monophosphate and protein kinase C responses. 859 91

The lack of control of tumour behaviour is manifested in different ways, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of "benign" tumours, like pituitary adenomas, in vitro studies are often used for evaluation of the tumour. The use of tissue explant cultures of human pituitary adenomas and the comparison of the feature of cultured tumours with their behaviour in vivo showed that corticotropin is released not only from the tumours associated with Cushing's disease, but also from clinically non-functioning tumours. Hence, it was supposed that the release of corticotropin in vivo from non-secreting tumours is probably under the influence of certain neuroendocrine and/or systemic humoral factors. To test this possibility, samples of 22 tumours were cultured in plain culture medium or in the presence of the "human plasma ultrafiltrate bioactive fraction" (tentatively termed as TBP) prepared by anion-exchange chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relatively high spontaneous secreting activity in vitro (> 200 ng/l in 24 hours), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated corticotropin release from tumours that showed relatively low basic corticotropin release (< 200 ng/l in 24 hours), with no obvious change in cellular corticotropin immunoreactivity. Such a dual activity of TBP was not observed for 8 samples of adenomas cultured in the presence of surrounding pituitary tissue, probably because TBP did not affect corticotropin secretion by the normal pituitary cells (as indicated by immunohistochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin release from pituitary adenoma tissue. Its possible involvement in the regulation of corticotropin release from normal pituitary tissue, however, is uncertain.
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PMID:Analysis of the in vitro secretory activity of human pituitary adenomas: modification of corticotropin release from adenoma tissue explant cultures by addition of a human plasma ultrafiltrate bioactive fraction. 870 30

The first gamma knife (GK) treatment of a pituitary adenoma in 1967 was meant as an alternative to the primitive surgical approaches that prevailed at the time, with consequent unsatisfactory results. Surprisingly, pituitary adenomas still account for only 7.8% of the 27,000 cases treated in GK centers worldwide. Transnasosphenoidal surgery has greatly improved and surgeons are reluctant to give up a relatively safe and effective operative technique. Radiosurgery is not currently vying to be the primary method of "surgery", but has a definite role following failed pituitary surgery and for tumors that extend into the cavernous sinus. Of 300 patients treated in our GK service, 30 had pituitary adenomas and most had undergone surgery. To date, we have not noted any side effects in the pituitary group. Published information is also reviewed and divided, where possible, into the pre-computed tomography (CT) era and the era of CT-magnetic resonance imaging (MRI). Growth hormone (GH)-secreting adenomas and prolactinomas tend to be larger and cannot be treated with the high doses successful against corticotropin (ACTH)-secreting tumors in Cushing's disease. Radiation fall-off is steep in GK radiosurgery, with the 20% isodose curve being only millimeters away from the point of maximal radiation. The effective dose has mostly been decided on the basis of maintaining safe levels at the sensitive perisellar neural structures. The safety of GK treatment (with no mortality and no permanent morbidity) is compared with other radiosurgical techniques. Good patient response owes much to the cumulative experience of GK pioneers and also to recent advances in images and computers that have enabled increasingly precise stereotaxic targeting and dose planning.
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PMID:Stereotactic radiosurgery of pituitary adenomas. 876 1

In a series of approximately 1,000 patients with pituitary adenoma who were operated on at our institution from 1970 to 1994, 932 were operated on for the first time. Most microadenomas were corticotropin (ACTH)-secreting, whereas all nonfunctioning adenomas were macroadenomas, reflecting internal surgical policy. Only 48 of 932 patients (5.1%) had transcranial surgery. Using stringent criteria for the definition of a cure, we obtained remission of disease in 54.9%, 87.3%, 66.7%, and 46.2% of all patients with growth hormone (GH)-, ACTH-, thyrotropin (TSH)-, and prolactin (PRL)-secreting adenomas, respectively. The good result in patients with Cushing's disease is related to the higher percentage of microadenomas (approximately equal to 80%) in this group. Unfavorable prognostic characteristics for all adenomas are increasing tumor size, invasiveness, infiltration, and high serum levels of the hypersecreted hormone. The absence of a reliable tumor marker makes it difficult to assess the results of surgery in patients with nonfunctioning pituitary adenoma, but normalization or improvement of visual defects occurred in 72.4% of patients. Permanent worsening of vision was detected in 2.2%, mostly operated on through the transcranial approach, but they had large tumors and so were at greater risk. Accordingly, there was a higher death rate in patients who received the transcranial operation (two of 48; 4.2%) than in patients operated on through the trans-sphenoidal route (seven of 884; 0.8%). However, between 1970 and 1980, the mortality rate was 1.6% (six of 367 patients), while between 1981 and 1994, it was 0.5% (three of 565 patients), stressing the importance of surgical experience and perioperative medical management in improving the safety of pituitary surgery.
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PMID:Surgical therapy of pituitary adenomas. 876 2

The effects of surgery on pituitary-gonadal function were investigated in women with pituitary adenomas other than prolactinomas. The subjects were 46 women of premenopausal age with a pituitary adenoma. Twenty tumors were GH producing, 19 were nonfunctioning, and 7 were adrenocorticotropin producing adenomas. The surgery was performed mainly via the transsphenoidal route, with the aim of eradicating the tumor and preserving pituitary function. The menstrual cycle was preserved postoperatively in 9 out of 10 (90%) patients with regular preoperative menstruation. Menstrual disturbance was seen in 36 (78.3%) cases preoperatively. The causative factors for menstrual disturbance were gonadotropin impairment and hyperprolactinemia in GH producing and nonfunctioning adenoma. Excessive hormonal secretion itself is a major causative factor for menstrual disturbance in GH and ACTH producing adenoma. Regular menstruation was restored following surgery in 20 out of 36 (55.6%) patients with menstrual problems. The predicting factors for postoperative recovery of menstruation are: size of adenoma less than 40 mm, period of amenorrhea less than 5 years, and preoperatively preserved gonadotropin secretion. In addition, preoperative hyperprolactinemia was also a predicting factor in women with nonfunctioning adenoma. Thus, even in patients with pituitary adenomas other than prolactinoma, the restoration of menstruation is highly achievable when surgery is performed with attention to preserving pituitary function.
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PMID:Effect of surgery on gonadal function of premenopausal women with pituitary adenomas other than prolactinomas. 879 26

Nelson's syndrome is a specific form of Cushing's disease treated by bilateral adrenalectomy, presenting with a deep hyperpigmentation caused by a pituitary adenoma (corticotropinoma). These ACTH-secreting tumors are frequently aggressive, so early diagnosis is of prime importance. We have studied 33 patients with Nelson's syndrome, 28 women and 5 men, aged 14-56 yr at the time of adrenalectomy and 16-58 yr at the time of Nelson's syndrome diagnosis (observed for 5-32 yr). Methods of examination included simultaneous adrenocorticotropic hormone (ACTH) and cortisol measurements during routine hydrocortisone replacement therapy, computed tomography (CT), pituitary magnetic resonance imaging (MRI), and visual field examination. The results obtained in a group of six patients diagnosed in the last 3 yr were compared with those obtained in a group of 27 patients examined before 1992. High plasma ACTH levels accompanied by normal serum cortisol concentration were characteristic for a late stage of the disease. Absolute temporal scotomas were an early finding. MRI, especially with the gadolinium enhancement, was superior to CT in demonstrating pituitary microadenomas in Nelson's syndrome. Thus, MRI diagnosis allowed for an early neurosurgical treatment of the patients with Nelson's tumors.
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PMID:Early diagnosis of Nelson's syndrome. 887 92

Cushing's disease and empty sella without evidence of pituitary adenoma are rarely observed. To our knowledge, there is very little documentation on long-term therapeutic follow-up with the steroidogenesis inhibitor ketoconazole. A 48-year-old woman with uncontrolled insulin-dependent diabetes mellitus, severe hypertension, and clinical findings of hypercortisolism was referred to our hospital. Endocrine evaluation of adrenocortical function evidenced hypothalamic-pituitary-hypercortisolism, and excluded adrenal tumor or an ectopic corticotropin source. Magnetic resonance imaging disclosed an empty sella turcica but not pituitary adenoma. The patient was treated with a steroidogenesis inhibitor, ketoconazole (600 mg daily) which reduced urinary cortisol excretion to within the normal range. Serum cortisol levels also returned to normal in the morning but not in the evening. The patient has continued on ketoconazole therapy for the past 7 years, with neither side effects nor tachyphylaxis. The reduction of cortisol secretion brought about significantly improved control of diabetes mellitus and hypertension, although signs of hypercortisolism have persisted. Radiographic studies of the hypophysis during follow-up have not evidenced adenoma.
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PMID:[Cushing's disease associated with empty sella: a clinical case treated for years with ketoconazole]. 907 69


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