Regulation of pituitary DNA synthesis during different reproductive states in the female rat: role of estrogens and prolactin (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.
Proceedings of the National Academy of Sciences, 1979
Male rats received acute or chronic primary or acute secondary stimulation with estradiol, and the effects on pituitary prolactin synthesis and its mRNA accumulation were examined. Prolactin synthesis was determined by the in vitro incorporation of [ 3 H]leucine into prolactin over a period of 1 hr. Prolactin mRNA was measured both by cell-free translation in a nuclease-treated rabbit reticulocyte lysate and by hybridization to the complementary DNA. The latter two methods gave similar results under all experimental conditions. Acute primary stimulation with estradiol produced a significant increase in pituitary prolactin mRNA accumulation at 12 hr, which further increased by 2- to 3-fold over the next 48 hr. In contrast, no increase in prolactin synthesis was observed during the first 24 hr. Chronic stimulation with estradiol induced increases of both prolactin synthesis and prolactin mRNA that were quantitatively indistinguishable over the period of 1-4 weeks, reaching a plateau a...
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.
Endocrine, 2008
The presence of folliculostellate cells in the anterior pituitary was described 49 years ago. These cells give about 10% of the whole cell population and through their long processes they provide intrahypophyseal communication. The folliculostellate cells contain S-100 protein. Its immunostaining was used to identify these cells. It was previously found that the diethylstilbestrol treatment basically influences the morphology and function of the trophic hormone secreting as well as the folliculostellate cells. In the present experiment, we have studied whether a concomitant progesterone treatment can prevent or attenuate changes caused by diethylstilbestrol treatment in the distribution of folliculostellate, prolactin, and GH cells. Diethylstilbestrol alone induced the appearance of prolactinomas. Inside the prolactinomas, folliculostellate cells were scattered but outside the prolactinomas they formed a demarcation line. Inside the prolactinomas, there were only a few growth hormone immunoreactive cells but they surrounded the prolactinomas in a ring-like pattern. When diethylstilbestrol was implanted with progesterone, the changes being characteristic for diethylstilbestrol treatment, could not develop. Concomitant progesterone influence prevented morphological changes in the anterior pituitary. Progesterone alone had no effect. In accordance with the formation of prolactinomas, the plasma prolactin level was very high in diethylstilbestrol treated rats. Concomitant progesterone treatment prevented the effect of diethylstilbestrol. Progesterone alone did not influence the prolactin level. GH levels did not significantly differ in any groups.
Hormonal Regulation of Prolactin Cell Development in the Fetal Pituitary Gland of the Mouse
Endocrinology, 2009
The developmental process of prolactin (PRL) cells in the fetal pituitary gland was studied in mice. Although PRL cells were hardly detectable in the pituitary gland of intact fetuses, a treatment with 17-estradiol (E 2 ) in vitro induced a number of PRL cells that varied drastically in number depending on the stage of gestation with a peak at embryonic d 15. This effect was specific to E 2, with epidermal growth factor, insulin, and forskolin failing to induce PRL cells. Although both estrogen receptor (ER)␣ and ER were expressed in the fetal pituitary gland, the results from ER knockout models showed that only ER␣ mediates E 2 action on PRL cells. A few PRL cells were observed in ER␣-deficient mice as well as in their control littermates, suggesting that estrogen is not required for the phenotype determination of PRL cells. Unexpectedly, the effect of E 2 on the induction of PRL cells in vitro was diminished after embryonic d 15. Present results suggest that the exposure of fetal PRL cells to glucocorticoids (GCs) results in a reduction of sensitivity to E 2 . The mechanism underlying the down-regulation of estrogen sensitivity by GCs was found not to be down-regulation of ER levels, induction of annexin 1, a GC-inducible inhibitor of PRL secretion, or a decrease in the number of PRL precursors by apoptosis. The effect of GCs appeared within 2 h and did not require a de novo protein synthesis. GCs are considered to be involved in the mechanisms of silencing pituitary PRL in gestation possibly through a novel mechanism.
Effect of prolactin on the steroidogenic response of rat luteal cells
Molecular and cellular …, 1984
The role of prolactin on some ovarian functions was studied in collagenase-dispersed luteal cells obtained from PMSG/hCG-primed rats. The in vitro effect of ovine prolactin (oPr1) on luteal cell function was assayed. This hormone produced a dose-dependent increase of progesterone production and an additive effect on hCG stimulation. oPr1 had no effect on CAMP production. Chronic effects of prolactin were studied in sulpiride (S), bromocriptine (Br) and oPrl-treated rats. Serum levels of prolactin were significantly higher in S-treated animals whereas Br administration rendered undetectable values. Serum progesterone was reduced in Br-treated animals and LH levels were similar in all groups studied. In vitro studies demonstrated a marked reduction of hCG stimulation of progesterone and CAMP production by luteal cells from hypoprolactinemic animals, while a significant increase was observed in hyperprolactinemic states. oPr1 and S treatment significantly increased ovarian LH binding sites while a reduction was observed in Br-treated rats. These data suggest that luteal cell function is regulated by circulating levels of prolactin and that this hormone has some direct effect on the steroidogenic process.
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.
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