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Query: UNIPROT:P06889 (Mol)
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The effect of castration and gonadal steroid replacement on the concentrations of LH-beta and alpha subunit and prolactin mRNA was examined in mice. Mouse LH-beta, alpha and prolactin mRNAs were approximately 0.8, 0.7 and 1.1 kb in size respectively. After ovariectomy, LH-beta mRNA levels increased 2- to 2.5-fold, while alpha mRNA levels increased 2.5-fold 6 and 10 days after ovariectomy. Serum LH rose after 2 days to reach six times control values at 10 days. Pituitary LH content doubled by 8 days after ovariectomy. Prolactin mRNA levels decreased to 50-60% of control at 3, 6, 8 and 10 days after ovariectomy and parallelled the fall in serum prolactin. Pituitary prolactin content fell more slowly, to 50% of intact control values by 10 days. The increase in both LH-beta and alpha subunit mRNA, and decrease in prolactin mRNA, and serum and pituitary hormone changes, after ovariectomy were prevented by oestradiol or oestradiol plus progesterone replacement. Levels of LH-beta mRNA increased more quickly in male than in female mice, the earliest change being seen 24 h after orchidectomy. Maximum values (two- to threefold) were found on day 6 after orchidectomy. Concentrations of alpha mRNA increased by 12 h to between 2 and 2.5 times control from 3 to 10 days after orchidectomy. Serum LH doubled by 12 h and was three to five times greater than control values up to 10 days. Pituitary LH content fell by 48 h before gradually increasing to intact values after 10 days. Prolactin mRNA levels decreased progressively from 2 days after orchidectomy, and this decrease was preceded by a fall in serum and pituitary prolactin which remained low throughout the experiment. Testosterone treatment attenuated the rise in alpha mRNA, prevented the rise in LH-beta mRNA and serum LH and partially restored the decrease in prolactin mRNA seen after orchidectomy. We conclude that in mice, as in rats and ewes, both LH-beta and alpha subunit mRNAs are negatively regulated by gonadal steroids, whereas prolactin mRNA is positively regulated, although there are temporal differences in patterns of mRNA responses between males and females. By comparison with female rats the rise in LH-beta mRNA after ovariectomy was slower in mice. Moreover, the discordant changes in pituitary LH content and LH subunit mRNAs seen in mice after castration were not observed in rats. Furthermore, pituitary prolactin and prolactin mRNA do not fall after orchidectomy of rats.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Endocrinol 1989 May
PMID:Regulation of LH subunit and prolactin mRNA by gonadal hormones in mice. 275 30

Pituitary thyrotroph cells specialize in the synthesis of TSH, and thus represent a model to study cell-specific gene expression. We have used the murine TSH beta (mTSH beta) gene promoter and TSH-producing and nonproducing transplantable tumors derived from murine thyrotroph cells, referred to as TtT-97 and MGH 101A, respectively, to identify nuclear factors which selectively interact with the mTSH beta gene. DNase I protection analyses demonstrate that factors present in TtT-97 nuclear extracts bind with high affinity to five separate sites in the TSH beta promoter region, denoted as distal D1 (-253 to -227) and proximal, P1 (-76 to -68), P2 (-106 to -98), P3 (-126 to -112), and P4 (-142 to -131) footprints. By contrast, non-TSH beta expressing thyrotroph cell nuclear extracts and L-cell nonpituitary cell extracts did not appear to footprint the D1 site; whereas the nonpituitary nuclear extracts revealed minimal DNase I protection in the P1-P4 regions. These data show that the distal D1 site is thyrotroph specific and contains a 6 base pair direct repeat sequence (5'-AGATAT-3'). Factor occupancy of the D1 site is protein dependent, occurs rapidly (less than 15 sec), is destabilized by 170 mM KCl, and results in an associated DNase I hypersensitive region. A double-stranded oligonucleotide spanning the D1 footprint competes only the distal factor binding region. Transfection of plasmid constructs containing progressive 5'-deletions of the mTSH beta promoter linked to the reporter gene luciferase into primary TtT-97 cells demonstrate a marked decrease in activity between the regions -270 and -79, which contains the D1 region.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Jul
PMID:Identification of thyrotroph-specific factors and cis-acting sequences of the murine thyrotropin beta subunit gene. 279 1

Immunoreactive (IR) POMC peptides have been detected in several human nonpituitary tissues and most pheochromocytomas and lung cancers, including those not associated with ectopic ACTH syndrome. We found IR-ACTH, IR-gamma MSH, IR-beta-endorphin (beta END), and IR-lipotropin in extracts from the following 10 normal human tissues, listed in order of decreasing POMC peptide concentrations: adrenal, testis, spleen, kidney, ovary, lung, thyroid, liver, colon, and duodenum. IR-ACTH, IR-gamma MSH, and IR-beta END were detected in all six pheochromocytomas and all 12 lung tumors (six squamous cell carcinomas, five adenocarcinomas, and one small cell carcinoma) we examined, as well as in a squamous cell carcinoma of the larynx. None of the patients had clinical evidence of ectopic ACTH syndrome. To determine whether these nonpituitary tissues and tumors actually synthesize POMC, rather than simply absorb POMC peptides from plasma, we examined poly(A) RNA prepared from these tissues and total RNA from pituitary by Northern blot hybridization for the presence of POMC-like mRNA with an exon 3 riboprobe. Pituitary contained a single POMC mRNA species of about 1150 bases. A short POMC-like mRNA of about 900 bases was found in all normal nonpituitary tissues, three of five pheochromocytomas, eight of nine lung cancers, and the laryngeal squamous cell tumor. In addition, larger POMC-like mRNA species between 1200 to 1500 bases were detected in adrenal, testis, ovary, placenta, two pheochromocytomas, and three squamous cell lung tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1988 Sep
PMID:Proopiomelanocortin gene is expressed in many normal human tissues and in tumors not associated with ectopic adrenocorticotropin syndrome. 284 57

Pituitary prolactin (PRL) cell microadenomata developed in females of a strain of Sprague-Dawley rats (SD1) following intragastric treatment with the carcinogenic hydrocarbon 7,12-dimethylbenz(a) anthracene (DMBA). Similar treatment of another strain of Sprague-Dawley rats (SD2) resulted in mammary tumour development but no PRL cell microadenomata. In SD1 strain rats morphologically distinct populations of PRL cells appeared after DMBA treatment, one composed of cells characterised by abundant, organised but very dilated RER and with large hormone storage granules, 500-600 nm in diameter (P1). The other cell type had electron-dense cytoplasm, narrow organised arrays of RER and moderately large, pleomorphic granules (P2). Both cell types appeared active with large Golgi and prominent nucleoli. P2 cells were most numerous 2 months after DMBA treatment but had virtually disappeared at 6 months and microadenomata were common at 8 months. PRL cells of SD2 rats were uniform in morphology, characterised by only moderate accumulations of RER, pleomorphic hormone storage granules, large Golgi and prominent nucleoli, and showed no close resemblance to either P1 or P2 cells of SD1 strain rats. It is possible that the morphological variations which developed in SD1 PRL cells may represent changes in responsiveness to factors controlling PRL cell secretion and proliferation and which may be pertinent to microadenoma development.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Prolactin cells of female rats treated with the carcinogen 7,12-dimethylbenz(A) anthracene (DMBA) in vivo. An ultrastructural study. 287 62

Three-day pituitary cell cultures from adult male and female rats were incubated for 4 h in the presence of 10 nM LHRH and the molecular heterogeneity of FSH was assessed in the media of LHRH-stimulated cells and in cell extracts from unstimulated cells using an electrofocusing technique. The pI distribution of FSH showed a high degree of similarity between cell media and cell extracts of each sex although differences were observed between sexes. Pituitary cell cultures from male rats were also incubated in the presence of 10(-8) M testosterone and 10(-8) M estradiol and the pI distribution of FSH from media after LHRH stimulation was determined. No significant differences in the pI profiles were observed. Incubation with charcoal-treated bovine follicular fluid (an inhibin source) resulted in a significant reduction in recovered FSH activity in the pH region 3.61-3.92 although this decrease did not markedly alter the pI profile of FSH. Close similarities were observed in the pI distribution of FSH of pituitary cell culture extracts and pituitary gland extracts from intact animals of both sexes, however, differences in pI distribution were noted in pituitary extracts in the male but not the female following gonadectomy. It is concluded that (1) stored FSH is released from the pituitary without major modification to its structure as assessed from its pI profile, (2) sex differences in the pI profile of FSH in pituitary extracts are retained in culture and following LHRH-stimulated release, (3) the pI distribution of FSH is not affected by testosterone or estradiol and only minimally by inhibin in short-term cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1985 Jul
PMID:Electrofocusing fractionation of follicle stimulating hormone in pituitary cell culture extracts from male and female rats. 299 Oct 42

Comparative studies on the release of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl) by the whole pituitary, pituitary plus hypothalamus and pituitary-hypothalamus complex (PHC) were undertaken to choose an appropriate model for studying the hypothalamus-pituitary interactions in vitro and to relate the importance of the intact neural connections between pituitary and hypothalamus on hypothalamus-pituitary interactions. Also the effect of including dopamine (DA) at 1 X 10(-7) mol/1 in these different in vitro systems on the release of LH, FSH and Prl was investigated. The pituitary released increasing amounts of LH and FSH at 2, 4 and 6 h but the amount of Prl released remained unchanged. The rates of release of LH, FSH and Prl by the pituitary were different and were characteristic of each hormone. Co-incubation of pituitary with hypothalamus stimulated the release of LH and FSH but inhibited the release of Prl. Pituitary-hypothalamus complex behaved almost identical to behaved almost identical to pituitary plus hypothalamus system. Inclusion of 1 X 10(-7) M DA in the incubation medium stimulated the release of LH (80%) but inhibited the release of Prl (71%) by PHC. FSH was unaffected. DA had no significant effect on the release of LH, FSH and Prl by pituitary and pituitary plus hypothalamus systems. It is suggested that PHC is the system of choice for studying hypothalamus-pituitary interactions in vitro.
Mol Cell Endocrinol 1986 Apr
PMID:The choice of a model for studying the hypothalamus-pituitary interactions in vitro. 308 18

Pituitary tumors induced by chronic diethylstilbestrol (DES) treatment in female F344 rats were treated subsequently with bromocriptine (BC). Effects of BC on separable subpopulations of lactotrophs were examined. Enzymatically dissociated cells from individual pituitaries were assessed regarding total number, relative lactotroph population, intracellular prolactin (PRL) content, PRL release in primary culture, and density alterations by separation in Ficoll-Hypaque or after sedimentation at unit gravity. In addition to the treatment and analysis of in situ tumors, the effects of BC treatment in vitro were assessed, using tumor cells which were first separated on Ficoll-Hypaque. Cell proliferation was assessed by cell cycle analysis, using DNA measurement by laser flow cytometry. BC treatment of tumors reversed the effects of DES on pituitary weight, PRL content and in vitro PRL release. Total cell recovery was not affected by BC, but cell separation showed that BC reduced the number of larger PRL-containing cells. Cell cycle analysis showed a decrease in numbers of cells in S and G2 cycle phases after BC in only one of four experiments. BC had an effect on proliferation in only the upper gradient fractions, containing the smallest cells. Culture of Ficoll-separated tumor cells revealed greater PRL release among lighter/smaller cells. BC treatment inhibited PRL release from both light and dense cells. The results establish that PRL cell hypertrophy, as well as hyperplasia, results from DES treatment. Bromocriptine treatment reverses this hypertrophy concomitant with inhibiting PRL synthesis and release. Reversal of proliferation in tumor cells is not a major effect of bromocriptine treatment.
Mol Cell Endocrinol 1988 Aug
PMID:Effects of bromocriptine on prolactin cellular hypertrophy, proliferation and secretory activity in diethylstilbestrol-induced pituitary tumors. 320 92

In the present study both the reverse hemolytic plaque assay for detecting luteinizing hormone (LH) secretion from single cells and LH immunocytochemistry (ICC) were applied to conduct quantitative studies on sexual differences in the gonadotrope population during postnatal development. Pituitary glands from both sexes at different ages were monodispersed with 0.1% trypsin. Freshly dispersed cells were incubated in Cunningham chambers in the presence of 10(-7) M gonadotropin-releasing hormone (GnRH) for measurement of the fraction of plaque-forming cells and the mean size of plaque formed, or attached to glass slides for measurement of the fraction of cells staining for LH by ICC. The percentage of immunostained LH cells increased with age in both sexes from about 5% of the total pituitary cell population at 5 days of age to a plateau of about 10% by 15 days and then fell to the adult level of about 5%. There were no significant sexual differences except at 30 and 40 days of age. In female rats the fraction of LH-secreting cells detected by plaque assay matched closely with that of LH-containing cells detected by ICC. However, there were significant sexual differences in the percentage of LH-secreting cells at day 15 through day 40. The mean LH output from individual cells of both sexes as indicated by the mean size of plaques also increased with age and reached a peak around 50 days. The sexual differences were first seen around 30 days of age with greater amounts in the female than in the male.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1988 May
PMID:Sexual dimorphism of pituitary gonadotropes during postnatal development in the rat. 329 58

Calcium is necessary for secretion of pituitary hormones. Many of the biological effects of Ca2+ are mediated by the Ca2+-binding protein calmodulin (CaM), which interacts specifically with proteins regulated by the Ca2+-CaM complex. One of these proteins is myosin light chain kinase (MLCK), a Ca2+-calmodulin dependent enzyme that phosphorylates the regulatory light chains of myosin, and has been implicated in motile processes in both muscle and non-muscle tissues. We determined the content and distribution of CaM and CaM-binding proteins in bovine pituitary homogenates, and subcellular fractions including secretory granules and secretory granule membranes. CaM measured by radioimmunoassay was found in each fraction; although approximately one-half was in the cytosolic fraction, CaM was also associated with the plasma membrane and secretory granule fractions. CaM-binding proteins were identified by an 125I-CaM gel overlay technique and quantitated by densitometric analysis of the autoradiograms. Pituitary homogenates contained nine major CaM-binding proteins of 146, 131, 90, 64, 58, 56, 52, 31 and 22 kilodaltons (kDa). Binding to all the bands was specific, Ca2+-sensitive, and displaceable with excess unlabeled CaM. Severe heat treatment (100 degrees C, 15 min), which results in a 75% reduction in phosphodiesterase activation by CaM, markedly decreased 125I-CaM binding to all protein bands. Secretory granule membranes showed enhancement for CaM-binding proteins with molecular weights of 184, 146, 131, 90, and 52,000. A specific, affinity purified antibody to chicken gizzard MLCK bound to the 146 kDa band in homogenates, centrifugal subcellular fractions, and secretory granule membrane. No such binding was associated with the granule contents. The enrichment of MLCK and other CaM-binding proteins in pituitary secretory granule membranes suggest a possible role for CaM and/or CaM-binding proteins in granule membrane function and possibly exocytosis.
Mol Cell Biochem 1987 Mar
PMID:Distribution of calmodulin and calmodulin-binding proteins in bovine pituitary: association of myosin light chain kinase with pituitary secretory granule membranes. 358 33

The pattern of human LH (hLH) microheterogeneity was determined using freshly obtained pituitary tissue. Chromatofocusing across a pH 9-6 gradient produced several, distinct peaks of hLH immunoreactivity between pH 8.5 and 6.8, as well as a 'salt peak'. Chromatofocusing of the 'salt peak' across a pH 7-4 gradient yielded distinct peaks of hLH at pH 6.1, 5.6, and 5.4. Pituitary tissue obtained at surgery produced a virtually identical pattern. By gel filtration the elution volume of each major chromatofocusing peak was similar to that of intact hLH, rather than those of the hLH subunits. The bioactivity/immunoreactivity ratios of the major chromatofocusing peaks fell dramatically with decreasing pH, from approximately 8 at pH 8.5 to approximately 1 at pH less than 6. These results indicate that human pituitary LH exists in multiple, isomeric forms that differ markedly in charge and bioactivity. These differences appear to be inherent in the native, intact molecules and not the result of autolysis or of dissociation into subunits.
Mol Cell Endocrinol 1987 Dec
PMID:Characterization of human LH isohormones from fresh pituitary tissue. 369 56


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