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

The failure of certain adrenal tumors to respond to ACTH was investigated in vivo be administration of corticotropin-(1-24)-tetracosapeptide (ACTH1-24) and dexamethasone and in vitro by studying the binding properties of ACTH1-24 and prostaglandin E1 (PGE1) and their effect on adenylate cyclase activity of the tumors' crude membranes; in addition, in five cases the stimulation of cortisol production in isolated adrenal cells by both hormones and dibuttyryl cyclic adenosine 3',5'-monophosphate (cAMP) was also studied. The results obtained in 13 hormone-producing tumors of the human adrenal cortex, i.e. 10 carcinomas and 3 adenomas, were compared with those found in normal human adrenal glands. According to the adenylate cyclase responses to ACTH1-24 and PGE1, the tumors fall into different categories. In the first group are six rumors in which the adenylate cyclase was stimulated by both ACTH1-24 and PGE; in addition specific binding could be demonstrated for the two hormones in all six. The binding affinity for 125I-ACTH1-24 was found to be about 10 times higher than that for 125I-ACTH11-24. In the one tumor in which the experiment was performed, bound 125I-ACTH1-24 was displaced by ACTH1-10. These results are similar to the ones found in normal human adrenal preparations. For two rumors of the group in which ACTH did not increase steroidogenesis in vivo, the biochemical abnormality might be located beyond cAMP formation. A second group encompasses six tumors in which the steroidogenesis in vivo and the adenylate cyclase activity were insensitive to ACTH1-24 but in which the enzyme was stimulated by PGE1 and NaF. However, these preparations bound 125I-ACTH1-24 and 125I-ACTH11-24, the binding affinity being similar for both peptides but 10 times lower than the one found in normal adrenal cortex for 125I-ACTH1-24. In the only case of this group where it was tested, ACTH1-10 did not displace bound 125I-ACTH1-24. This result strongly suggests the possibility of a modification or a loss of the receptor site that binds the N-terminal sequency (1-10) of ACTH, the biologically active part of the molecule. In the last tumor, both PGE1 and ACTH were unable to stimulate adenylate cyclase activity and steroid production in a preparation of isolated adrenal cells, although steroidogenesis was stimulated by dibutyryl though steroidogenesis was stimulated by dibutyryl cAMP. No specific binding for PGE1 could be demonstrated. However, 125I-ACTH1-24 and 125I-ACTH11-24 were found to be bound to the tumor with the same affinity.
 ...
PMID:ACTH and prostaglandin receptors in human adrenocortical tumors. Apparent modification of a specific component of the ACTH-binding site. 16 92

The ability of melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and prostaglandin E1 (PGE1) to stimulate the accumulation of cyclic AMP was examined in intact mouse melanoma cells of varying metastatic potential. F1 cells (low metastatic potential) had significantly greater cyclic AMP levels in response to all three hormones than F5 (intermediate metastatic potential) and F10 (high metastatic potential) cells. The ranking of the response was as follows: MSH, F1 greater than F5 greater than F10, ACTH, F1 greater than F5 greater F10, PGE, F1 greater than F10 greater F5. In contrast to the above, the degree of hormonal stimulation of adenylate cyclase in broken cell preparations was virtually identical in all three melanoma cell lines. Control enzyme activity was depressed in both F5 and F10 relative to F1. The conflicting results between studies of intact vs. broken cell preparations could not be explained by increased cyclic AMP phosphodiesterase activity in F5 and F10 cells. We conclude that as the melanoma cells increase in metastatic potential, there is a significant loss in the ability of their cyclic AMP system to respond appropriately to hormonal stimuli.
 ...
PMID:Hormonal activation of adenylate cyclase in mouse melanoma metastatic variants. 20 54

An ideal in vitro model for the study of endocrine functions would be one in which cells could propagate in culture and express their specialized functions. Most endocrine studies to date have relied on primary cell culture or on the use of tumor cell lines. This report describes the characterization of three endocrine cell lines immortalized by transfecting endocrine cells with a temperature-sensitive mutant SV40 virus. Rabbit endometrium (HRE-H9), human placenta (SPA209-10) and rat pituitary (RP) cells were immortalized by SV40 virus, a temperature-sensitive (ts) mutant in the A gene, which encodes the large tumor antigen that is required for the maintenance of transformation. The transformed phenotype of the SV40 tsA mutant-immortalized cell line can be reversed simply by a shift in temperature. At the permissive temperature (34 degrees C), all three types of cells exhibited a transformed phenotype, which is characterized by high cell density growth and by the overgrowth of nontransformed cell layers. However, at the non-permissive temperature (40 degrees C) these cells reverted to a non-transformed phenotype as demonstrated by a marked decrease in the overgrowth of nontransformed layers and by the expression of differentiated functions. At the non-permissive temperature (40 degrees C), the endometrial cell line was capable of synthesizing beta-endorphin, and it exhibited hormonally regulated expression of the transfected hybrid uteroferrin gene construct. The human placenta cell line was capable of secreting GnRH upon stimulation by cAMP, forskolin, theophyllin, PGE, catecholamine and Ca++ channel stimulators. Moreover, the rat pituitary cell line was capable of synthesizing and secreting growth hormone (GH) which was stimulated by GHRH and cAMP. The advantage of the temperature-sensitive cell lines is that a single cell line is the source of both the normal and transformed states; thus, studies are internally controlled. These results demonstrate that tsA mutants of SV40 virus are the best available agents for immortalizing mammalian endocrine cells that retain differentiated functions.
 ...
PMID:Characterization of endocrine cell lines immortalized by a temperature-sensitive mutant SV40. 165 33

The role of prostaglandin E2 (PGE2) on the mechanism of corticotropin releasing factor (CRF) induced adrenocorticotropin (ACTH) release was studied in primary rat pituitary cell culture. The continuous incubation of pituitary cells with PGE2 inhibited CRF-stimulated ACTH with an ED50 of 1.2 X 10(-9) M PGE2. PGE2, however, did not alter the spontaneous release of ACTH. PGE (10(-8) M) significantly decreased 10(-10) M, 10(-9) M, and 10(-8) M CRF-mediated ACTH release by 42%, 47%, and 31% of total CRF stimulated ACTH release. Time course experiments demonstrated a PGE2-induced inhibition by 20 min of CRF incubation which continued for 3 h. After a 2-h incubation with PGE2, the wash-out of PGE2 from the culture medium just prior to the addition of CRF eliminated the inhibitory activity of PGE2. PGE2 decreased the amount of CRF-stimulated ACTH from cells incubated with cycloheximide (P less than 0.01). The inhibitory activity of PGE2 (10(-8) M) on CRF-stimulated ACTH was unaltered by the addition of 3 mM or 7 mM CaCl2 to the standard culture media (1.6 mM CaCl2). The inhibition of CRF-induced ACTH release by maximal inhibitory concentrations of PGE2 (10(-7) M) and cortisol (5 X 10(-7) M) were not additive. In conclusion, PGE2 may play an important role in modulating pituitary ACTH release. Its inhibitory activity occurs by 20 min of CRF incubation, is in part independent of protein synthesis, requires the continued presence of PGE2, is not reversed with CaCl2, and is not additive with the inhibitory activity of cortisol.
 ...
PMID:Characterization of PGE2 inhibition of corticotropin releasing factor-mediated ACTH release. 303 58

Prostaglandins and their C20:(omega)6 fatty acid precursors are present in rat adrenal glands. Small doses of prostaglandins (PGE(1), PGE(2), or PGF(1infinity) 1.4 to 2.4 micromolar) increased steroidogenesis in the superfused adrenal glands obtained from hypophysectomized rats. This effect was mimicked in part by both adrenocorticotropin and its postulated intracellular intermediate adenosine 3', 5'-cyclic monophosphate; all three responses were inhibited by cycloheximide.
 ...
PMID:Prostaglandin stimulation of rat corticosteroidogenesis. 430 81

Prostaglandins E(1) and E(2) significantly stimulated the synthesis of aldosterone, corticosterone, and to a lesser degree, cortisol in the outer slices of beef adrenal tissue. PGA, PGF(1a), and PGF(2a) were ineffective.PGE(1) was found to stimulate steroidogenesis in a manner similar to that of adrenocorticotropin (ACTH) in (a) needing calcium, (b) being inhibited by puromycin but not actinomycin D, (c) increasing the levels of cyclic AMP, and (d) not having an additive effect to exogenous cyclic AMP. PGE(1) did not produce an additive effect with either submaximal or maximal amounts of ACTH but did have an additive effect with angiotensin. These results are in keeping with the hypothesis that PGE(1) shares a receptor site on the plasma membrane with ACTH.
 ...
PMID:Adrenocortical steroidogenesis: the effects of prostaglandins. 434 27

We have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE(1), PGE(2)) stimulation of thyroidal adenyl cyclase activation and cyclic 3',5'-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE(1) and PGF(2alpha) showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE(1)-(3)H and PGF(2alpha)-(3)H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE(1)-(3)H and PGF(2alpha)-(3)H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE(1) and PGF(2alpha) "equivalents" varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37 degrees C. TSH, 10-100 mU/ml, increased the levels of cell PGE(1) and PGF(2alpha) "equivalents" 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE(1) or PGF(2alpha) "equivalent" levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.
 ...
PMID:Thyrotropin increases prostaglandin levels in isolated thyroid cells. 462 70

We explored the action of beta-endorphin (beta E) and naltrexone (Nal) on the number of oocytes and on prostaglandins (PGE and PGF2 alpha) production by the ovaries from PMSG/hCG-primed immature and cycling rats. Superovulated rats were injected with beta-endorphin (0.5 microgram) intraperitoneally 4 hours after hCG. The number of ova ovulated was inhibited and this effect was blocked with naltrexone injected into the ovarian bursa (0.1 microgram) 30 minutes before beta-endorphin. Furthermore, beta-endorphin (10(-8) M) decreased prostaglandins production by ovaries isolated 4 hours after hCG. Intraperitoneal injection of beta-endorphin (0.5 microgram) at 17:00 hr on proestrus decreased (-23%) the number of ova within oviducts on the day after (estrus). Naltrexone injected intraperitoneally (5 micrograms) at 16:30 hr on proestrus increased the number of ova (+23%). On the other hand, beta-endorphin increased the number of oocytes obtained by puncture of antral follicles (+37%) and naltrexone decreased the number of oocytes (-33%). Prostaglandins content in the ovary of adult rats at 23:00 hr, approximately 4 hr before the onset of ovulation, was diminished when the rats received beta-endorphin at proestrus. Moreover, when the rats were injected with naltrexone, ovarian production of prostaglandins was increased. Our results further support the hypothesis that beta-endorphin affects ovulation at the level of the ovary in the rat and that endogenous opioids may be modulating this physiological process.
 ...
PMID:Naltrexone enhances ovulation and prostaglandin synthesis in the rat ovary. 937 81

Human spaceflight is associated with a chronic loss of protein from muscle. The objective of this study was to determine whether changes in urinary hormone excretion could identify a hormonal role for this loss. Urine samples were collected from the crews of two Life Sciences Space Shuttle missions before and during spaceflight. Data are means +/- SE with the number of subjects in parentheses. The first value is the mean preflight measurement, and the second value is the mean inflight measurement. Adrenocorticotropic hormone (ACTH) [27.7 +/- 4.4 (9) vs. 25.1 +/- 3.4 (9) ng/day], growth hormone [724 +/- 251 (9) vs. 710 +/- 206 (9) ng/day], insulin-like growth factor I [6.81 +/- 0.62 vs. 6.04 +/- 0.51 (8) nM/day], and C-peptide [44.9 +/- 8.3 (9) vs. 50.7 +/- 10.3 (9) micrograms/day] were unchanged with spaceflight. In contrast, free 3,5,3'-triiodothyronine [791 +/- 159 (9) vs. 371 +/- 41 (9) pg/day, P < 0.05], prostaglandin E2 (PGE2) [1, 064 +/- 391 (8) vs. 465 +/- 146 (8) ng/day, P < 0.05], and its metabolite PGE-M [1,015 +/- 98 (9) vs. 678 +/- 105 (9) ng/day, P < 0. 05] were decreased inflight. The urinary excretion of most hormones returned to their preflight levels during the postflight period, with the exception of ACTH [47.5 +/- 10.3 (9) ng/day], PGE2 [1,433 +/- 327 (8) ng/day], PGF2alpha, [2,786 +/- 313 (8) ng/day], and its metabolite PGF-M [4,814 +/- 402 (9) ng/day], which were all increased compared with the preflight measurement (P < 0.05). There was a trend for urinary cortisol to be elevated inflight [55.3 +/- 5. 9 (9) vs. 72.5 +/- 11.1 micrograms/day, P = 0.27] and postflight [82.7 +/- 8.6 (8) micrograms/day, P = 0.13]. The inflight human data support ground-based in vitro work showing that prostaglandins have a major role in modulating the changes in muscle protein content in response to tension or the lack thereof.
 ...
PMID:Endocrine relationships during human spaceflight. 988 62

The purpose of this study was to investigate the effect of corticotropin-releasing hormone (CRH) on the expression of the prostaglandin (PG) E(2) EP1 receptor subtype and PGE(2) production in amnion WISH cells (AWC). AWC cultures were incubated with CRH. Culture fluid was collected for PGE(2) measurement, and the cells were collected and analyzed for EP1 protein and mRNA. Immunohistochemical localization of the EP1 receptor was also performed. Incubation of AWC with CRH resulted in a dose-dependent increase (r = 0.97) in the level of EP1 receptor protein (P < 0.001). Coincubation of AWC with CRH and indomethacin resulted in the decreased production of PGE(2) while having no effect on EP1 receptor expression. A significant but not dose-dependent increase in EP1 mRNA expression was also observed (P < 0.01). Immunohistochemical evaluation verified cell membrane localization of the receptor in both stimulated and unstimulated cells and confirmed the increased expression of EP1 receptor in response to CRH. Incubation of AWC with CRH also resulted in increased culture fluid PGE(2) levels (P < 0.01). These results suggest that the role CRH plays in the initiation of labor may also involve the promotion of elevated PGE(2) levels and increased expression of the EP1 receptor in amnion.
 ...
PMID:Corticotropin-releasing hormone increases the expression of the prostaglandin E(2) receptor subtype EP1 in amnion WISH cells. 1061 Oct 63


1 2 3 Next >>