Comparison of primary and secondary stimulation of male rats by estradiol in terms of prolactin synthesis and mRNA accumulation in the pituitary (original) (raw)
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Journal of Endocrinology, 1982
The effect of daily injections of sulpiride was compared with that of a single injection of the drug in male rats which had been treated with oestradiol diundecenoate for various periods of time. We studied the effect of the different treatments on weight of the pituitary gland, concentration of prolactin and incorporation of [3H]thymidine into DNA in the pituitary gland and on serum levels of prolactin. Administration of the oestrogen produced a marked increase in the synthesis of DNA at day 7. The stimulation diminished at day 21 and was not significant at day 45. The maximum increase in the concentration of prolactin in serum and pituitary glands was observed during the first 7 days (approximately 400 and 150% respectively) and in the weight of the anterior pituitary gland after 21 days of treatment (approximately 107%). A single injection of sulpiride markedly stimulated the release of prolactin and the synthesis of DNA at day 7. Both these effects diminished at day 21 and disappeared by day 45. Daily injections of sulpiride also produced similar changes in the release of prolactin and in the replication of DNA. The growth of the anterior pituitary gland was greater in this group than in the rats which had been treated with oestradiol diundecenoate only. After the end of treatment with oestrogen and sulpiride the pituitary weight and the concentration of prolactin in the anterior pituitary gland diminished together with levels of prolactin and oestrogen in serum. There was a good correlation between weight of the gland and serum levels of prolactin. The results further support the idea of a mechanism which controls the proliferation of lactotrophs in which the release of the hormone is accompanied by an increase in pituitary DNA synthesis.
Androgen metabolism and mechanism of action in prolactin secreting rat pituitary cells in culture
Journal of Steroid Biochemistry, 1982
The effects of different androgens on prolactin (PRL) synthesis were studied in clonal strains (GH3, GH4) of rat pituitary tumour cells. PRL synthesis was measured as the amount of hormone which accumulated in the culture m~ium during 24 h (~g/mg cell protein/24 h). The GH3 cdls are known to metabolize testosterone rapidly and extensively (-90%). So-~ihydrotestosterone (DHT) (55%) and 5a-androst~e-3~,17~~ioi (3&dioi) (31%) constituted the major metabolites, while no conversion of testosterone to oestrogens was observed (Aakvaag and Haug, J. steroid Biockem. 11, 1979, 1341-1346). Testosterone, DHT, 3&d'ml, Sa-androstane-3~,17~-dial (3a-dial) and 4-androstene-3,17-dione (A4-A) all stimulated PRL synthesis in a dose-dependent manner. The stimulatory effects were observed at about lOA M and the maximum effects were found at about 5 x 10e6 M. 3&Diol was invariably the most potent stimulator and caused a 2-3 fold increase in PRL synthesis. DHT and testosterone were almost equally potent, but they were on a molar basis only half as effective as 3/3-diol in stimulating PRL synthesis. 3cl-Diol was almost as potent as the 3fi-epimer, while M-A caused only a very slight increase in PRL synthesis. None of the androgens influenced cell growth measured as cell protein content per culture dish. The synthetic Se-reductase inhibitor 4-androsten-3one,l7~-carboxylic acid (androstene-17/S-C 3H) inhibited the conversion of testosterone to its 5x-reduced metabolites (DHT, 3@-dial and 3a-diolr without any effect on PRL synthesis or cell growth. After 40 h incubation more than 90% of the added radioactivity was recovered as intact E3H]-testosterone in the presence of androstene-17~-COOH (4 x IOe5 M) as compared to only 35% in the control cultures. The finding that testosterone was equally potent in stimulating PRL synthesis in the absence or presence of androstene-17~-COOH suggested that the effect of testosterone on PRL synthesis was independent of its %-reduction. The stimulating effect of testosterone and DHT on PRL synthesis was equal to that of the synthetic androgen methyltrienolone (R 1881). This study shows that testosterone and its %-reduced metabolites DHT, 3/I-diol and 3a-diol stimulated PRL synthesis dose-dependently in the GHJ cells, and the effect of testosterone was not dependent on its Se-reduction. 1.
Common and specific effects of the two major forms of prolactin in the rat testis
AJP: Endocrinology and Metabolism, 2007
Prolactin (PRL) has both stimulatory and inhibitory effects on testicular function, a finding we hypothesized may be related in some part to the form of the hormone present or administered. In the analysis of the pituitary secretion profiles of early pubescent vs. mature male rats, we found PRL released from early pubescent pituitaries had about twice the degree of phosphorylation. Treatment of mature males with either unmodified PRL (U-PRL) or phosphorylated PRL (via the molecular mimic S179D PRL) for a period of 4 wk (circulating level of ∼50 ng/ml) showed serum testosterone decreased by ∼35% only by treatment with the phospho-mimic S179D PRL. Given the specificity of this effect, it was initially surprising that both forms of PRL decreased testicular expression of 3β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein. Both forms also increased expression of the luteinizing hormone receptor, but only S179D PRL increased the ratio of short to long PRL receptors...
Endocrinology, 2008
Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin’s signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Las...
Molecular Endocrinology, 1990
Regulation by PRL of aromatase (P450arom) mRNA and protein and estradiol (E) biosynthesis was examined in granulosa cells during early stages of luteinization in vitro and in vivo. PRL caused a dosedependent (10-1000 ng/ml) decrease in P450arom mRNA and E biosynthesis (>99%) in luteinized rat granulosa cells in vitro, even when the cells were cultured in the presence of insulin and hydrocortisone (hormones known to synergize with PRL to induce proteins in mammary tissue) or in the presence of forskolin (a nonhormonal stimulator of cAMP). PRL also prevented the marked increases in aromatase mRNA and E biosynthesis stimulated by FSH and forskolin in nonluteinized preovulatory granulosa cells in culture. These effects of PRL on granulosa cells in culture were specific for aromatase and were not observed for other proteins, such as cholesterol side-chain cleavage cytochrome P450 (P450scc) and a 2-macroglobulin. PRL also decreased P450arom mRNA and protein during the early stages of luteinization in vivo. PRL administered to rats beginning day 1 postovulation to mimic hormone release during pseudopregnancy reduced the progressive increase in P450arom mRNA occurring in corpora lutea on days 3-4 in ovulated rats not treated with PRL. CB 154, a dopamine agonist that inhibits pituitary release of PRL, caused P450arom mRNA and protein to decrease 50% if given to pregnant rats on days 8-10 of gestation, but increased P450arom mRNA and protein if given to pregnant rats on days 10-12 of gestation. These diverse effects of PRL in pregnancy suggest that placental factors may modify the response of luteal cells to PRL during gestation. Taken together, the results of these studies provide the first unequivocal evidence that pituitary PRL can act to inhibit aromatase mRNA and E biosynthesis in granulosa cells of rat preovulatory follicles before and during the early stages of luteinization. Our results demon
Estrogen regulation of the rat anterior pituitary gland proteome
Experimental biology and medicine (Maywood, N.J.), 2005
Estrogen is known to affect the regulation of all six of the established anterior pituitary gland (AP) hormones, but little is known of the specifics of its regulation of the AP hormones, their isoforms, and nonhormonal AP proteins. We used difference gel electrophoresis in conjunction with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass fingerprinting to quantify the effects of estrogen on the AP-soluble protein fraction in rats. Two-month-old rats were ovariectomized and used at 6 months of age. They were injected subcutaneously with sesame oil vehicle or 50 lg estradiol valerate in vehicle and studied 48 hrs later, approximately 3 hrs before the time of the anticipated onset of the estrogen-induced surges of gonadotropins in blood. The APs were pooled, and the soluble protein fraction was examined in replicate analyses. After DeCyder software analysis, we identified 26 protein spots that had a 1.5-fold or greater average increase in the experimental group relative to the controls. Nineteen showed a 1.5-fold or greater decrease. Estrogen increased levels of the more acidic isoforms of growth hormone and prolactin and of proteins involved in protein synthesis, folding, and secretion (e.g., eukaryotic translation elongation factor 2, ERp57, ERp29, Hsc70-ps1, calreticulin, coatomer delta subunit, and secretogranin II) and of some metabolic enzymes (e.g., arginosuccinate synthetase, enolase 1, creatine kinase B, phosphoglycerate mutase, malate dehydrogenase, pyruvate kinase, and aldolase A). The majority of the downregulated proteins were involved in RNA or DNA interactions (e.g., five heterogeneous nuclear ribonucleoproteins, DEAD-box proteins 17 and 48, ssDNA binding protein PUR-alpha, PTB-associated splicing factor, and Pigpen protein), but isovaleryl coenzyme A dehydrogenase, mitochondrial aldehyde dehydrogenase, stathmin 1, vinculin, radixin, and secretogranin III were also reduced.
The Journal of Cell Biology, 1980
The secretion of prolactin in cultured pituitary cells was studied in correlation with the cellular changes induced by stimulatory or inhibitory agents. The techniques used in this study were: radioimmunoassay, immunocytochemistry, scanning (SEM) as well as transmission (TEM) electron microscopy. Prolactin secretion was stimulated by 17 beta-estradiol (10 nM) as well as thyrotropin-releasing hormone (TRH) (3 nM) and inhibited by 2-Br-alpha-ergocryptine (CB-154) (1 muM). The total prolactin (release and cell content) increased between 2 and 8 d of estradiol treatment, indicating an increase of both synthesis and release of prolactin. This finding was in agreement with TEM observations because, in estradiol-treated prolactin cells, the Golgi saccules were distended and Golgi elements were increased, thus indicating increased synthetic activity of these cells. The addition of TRH over a 4-h period resulted in a significant degranulation of prolactin cells. In contrast, prolactin secret...