Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to further characterize the regulation of LH/hCG receptors by FSH in granulosa cells and test the hypothesis that the LH/hCG receptor levels are heteroregulated by PRL. Granulosa cells from immature hypophysectomized, DES-treated rats were cultured for 2-4 days in defined medium containing androstenedione (10(-7) M) and/or FSH and PRL, after which [125I]iodo-hCG binding to the granulosa cells was measured. When granulosa cells were cultured for 2 days (days 0-2) with increasing concentrations of FSH (0.1-100 ng/ml), there was a dose related increase in [125I]iode-hCG binding from a control value of 1.05 +/- 0.2 fmoles/10(6) cells to a maximum of 20 +/- 1.8 fmoles/10(6) cells. The miminum, half-maximum (ED50) and maximum doses of FSH were 0.3, 0.5 and 3 ng/ml, respectively. At concentrations of FSH greater than 3 ng/ml there was a progressive decrease in [125I]-iodo-hCG binding to a low value of 6.1 +/- 1 fmoles/10(6) cells at 100 ng/ml of FSH. No changes in [125I]iodo-hCG binding were observed in response to PRL (1 microgram/ml) during the day 0-2 incubation. When granulosa cells were stimulated for 2 days with 20 ng/ml of FSH, washed, and then recultured for another 2 days (days 2-4) with FSH, the LH/hCG receptor content remained high (F leads to F = 17.4 +/- 2.8 fmoles/10(6) cells). In contrast, when FSH-primed cells were recultured for 2 days without FSH, the [125I]iodo-hCG binding decreased sharply to near control levels (F leads to C = 2.5 +/- 0.2 fmoles/10(6) cells). This marked loss of LH/hCG receptors was largely prevented when FSH primed cells were recultured with PRL (F leads to P = 10.3 +/- 1.5 fmoles/10(6) cells). This stimulatory effect of PRL on [125I]iodo-hCG binding was dose-dependent: minimum, ED50, and maximum doses of PRL were 0.2, 0.5 and 1 microgram/ml, respectively. Scatchard-plot analysis revealed that although the dissociation constant (Kd) of the LH/hCG receptors stimulated by FSH and PRL were of similar high affinity (approximately 8 x 10(-11) M), the maximum binding (Bmax) values in the PRL-treated cells were less. Addition of 10(-7) estradiol together with the PRL did not cause a further increase in Bmax values above that observed with PRL alone.
Mol Cell Endocrinol 1981 Aug
PMID:In vitro heteroregulation of LH receptors by prolactin and FSH in rat granulosa cells. 626 71

The role of cyclic AMP in the induction of enzymes involved in estrogen and progestin biosynthesis in undifferentiated granulosa cells was investigated. When granulosa cells from immature hypophysectomized, DES-treated rats were cultured for 2 days in serum-free medium with aromatase substrate (10(-7) M androstenedione) together with graded doses of FSH, prostaglandin E2 (PGE2), cholera toxin (CT), or dibutyryl cyclic AMP (Bu2cAmP), there was a dose-related increase in estrogen (E) production. The induction of E production by saturating doses of FSH, PGE2, CT, and Bu2cAmP required a lag phase of approximately 24 h, after which the E response increased sharply to maximum levels at day 3, and then declined gradually to day 5. Treatment for 24 h ((day 0-1) with FSH, together with 1 microgram/ml of either actinomycin D or cycloheximide, completely abolished the stimulatory action of FSH on E production. When the inhibitors were removed, the FSH-induced increases in E returned to near normal levels after a 24-h lag period. Similar effects of the inhibitors upon E production by CT, PGE2 and Bu2cAMP were observed. As with E, the production of progesterone and 20 alpha-dihydroprogesterone was markedly stimulated by FSH, PGE2, CT and Bu2cAmP, and the results of the time course, dose response, and inhibitor experiments were similar to those for E production. These results indicate that FSH induces the de novo synthesis of enzymes required for both estrogen and progestin biosynthesis by undifferentiated granulosa cells and suggest that this action is mediated by cyclic AMP.
Mol Cell Endocrinol 1982 Jan
PMID:The role of cyclic AMP in the induction of estrogen and progestin synthesis in cultured granulosa cells. 627 57

Fluid from large (6-12 mm) porcine follicles (LFFl) enhanced estrogen secretion by granulosa cells from small (1-2 mm) antral porcine follicles during 3-day incubations. Shorter incubations with LFFl or of any length with fluid from small follicles were inconsistent in elevating estrogen secretion. Estrogen was undetectable in freshly collected cells. Addition of 0.14-0.7 micrograms/ml androgens increased estrogen secretion but addition of androgen in a concentration equivalent to that in charcoal-treated LFFl (140 pg/ml) did not. FSH stimulated progesterone but not estrogen secretion. Pretreatment with FSH did not enhance LFFl stimulation of aromatase activity, nor did pretreatment with LFFl influence FSH action on aromatase. These observations suggest the presence of an aromatase stimulator in fluid from nonatretic follicles. By stimulating estrogen production the factor might contribute to follicle development and prevent an increase of the androgen/estrogen ratio which has been proposed to influence atresia.
Mol Cell Endocrinol 1983 Feb
PMID:Follicular fluid stimulation of estrogen secretion by immature porcine granulosa cells. 640 95

Estrogen receptors are present in cytosol prepared from the accessory sex organs (vesicular gland, proprostate, prostate, bulbourethral gland) of sexually immature and of sexually mature rabbits. The receptor in these organs from animals of both age groups has a sedimentation coefficient of 8-10S on low ionic strength (0.01 M KCl) sucrose gradients. Under high ionic strength (0.4 M KCl) conditions, the receptor sediments at approximately 4S. The cytoplasmic estrogen receptor from the epididymis shows age-dependent changes in its sedimentation coefficient. It is 8S under low ionic strength conditions when prepared from immature rabbits and 4S under identical conditions when prepared from sexually mature animals. Although the dissociation constant of the cytoplasmic estrogen receptor in the immature and mature epididymis and accessory sex organs remains constant during development (approximately 0.1 nM), the number of available cytoplasmic estrogen binding sites declines from about 160 fmoles/mg cytosol protein in the immature rabbit to about 40 fmoles/mg cytosol protein in the adult animal. The estrogen receptor in the accessory sex organs is highly specific, the relative affinities of various potential competitors being: estradiol and estrone = 1, diethylstilbestrol = 0.3, estriol = 0.2, tamoxifen = 0.08, testosterone = 0.0004 and 5 alpha-DHT = 0.00005. Changes with age in the physicochemical characteristics of the estrogen receptor and in the concentration of binding sites suggest that the estrogen receptor may be involved in the development and physiological regulation of the male reproductive tract.
Mol Cell Endocrinol 1983 Dec
PMID:Identification of cytoplasmic estrogen receptors in the accessory sex organs of the rabbit and their comparison to the cytoplasmic estrogen receptor in the epididymis. 665 71

We studied DNA synthesis in the rat adenohypophysis during the estrous cycle, pregnancy and lactation. During the estrous cycle, DNA synthesis was 3 times higher on the morning of estrus than on the other days. This peak was abolished completely by ovariectomy or pentobarbital, which also blocked the preovulatory surges of LH and prolactin. Methallibure , which blocked the LH but not the prolaction surge, had a partial effect on DNA synthesis. An acute and significant decrease in pituitary DNA synthesis occurred between days 0 (estrus) and 1 of pregnancy, followed by a less pronounced diminution until parturition. After delivery, DNA synthesis increased steeply on day 1 of lactation, returning to low values by day 3, under normal suckling conditions. Thelectomy , which blocked suckling-induced prolactin release, or antiestrogen treatment, which did not decrease prolactin secretion, diminished pituitary DNA synthesis on day 1 of lactation. Estrogen administration to intact or ovariectomized rats on days 9-11 of lactation stimulated (100%) DNA synthesis. Ovariectomy had no effect. In conclusion, in the different reproductive states studied, pituitary DNA synthesis is related to prolactin release in the presence of estrogens.
Mol Cell Endocrinol 1984 May
PMID:Regulation of pituitary DNA synthesis during different reproductive states in the female rat: role of estrogens and prolactin. 673 26

It has been hypothesized that progesterone (P) exerts a direct inhibitory effect on ovarian follicular development, an effect which could be mediated by P receptors located in granulosa cells. We tested this hypothesis by examining the effect of several progestins on FSH-stimulated estrogen (E), P, and 20 alpha-dihydroprogesterone (DHP) production by cultured rat granulosa cells, and correlated the results with the ability of the progestins to bind to the granulosa cell P receptor. Granulosa cells from immature hypophysectomized DES-treated rat produced 9 ng/ml E, 21 ng/ml P and 29 ng/ml DHP during a 2-day incubation in McCoy's 5a medium containing 10(-7) M androstenedione and 10 ng/ml of FSH. The FSH-induced increase in E production was inhibited by 50 and 95% following concomitant treatment with 3 x 10(-6) and 10(-5) M resp. of R5020, a potent synthetic progestin. Added R5020 at these concentrations also significantly inhibited P and DHP production. R5020 had no effect on granulosa cell viability or plating efficiency, and the inhibitory action of R50920 on E production was reversible. In studies of the specificity of the progestin inhibitory action, the relative abilities of various progestins to inhibit E production were R5020 > P > DHP > 17 alpha-hydroxyprogesterone (17OHP). The relative abilities of these progestins to bind to the ovary P receptor were also: R5020 > P > DHP > 17OHP. These results indicate that exogenous progestins directly inhibit the FSH-stimulation of granulosa cell steroidogenesis in vitro and suggest that the progestin effect may be mediated by the P receptor. Such results offer a possible mechanism whereby progesterone could exert a direct but reversible inhibitory action on ovarian follicular development.
Mol Cell Endocrinol 1980 Aug
PMID:Progestins inhibit FSH-stimulated steroidogenesis in cultured rat granulosa cells. 677 34

The effect of prolactin (PRL) treatment on estrogen production by rat granulosa cells was investigated in vitro. Immature, hypophysectomized, DES-treated rats were injected for 2 days with FSH to induce aromatase enzymes and receptors for PRL and LH. After FSH priming, the granulosa cells were cultured for 4 days in serum-free medium containing 10(-7) M androstenedione and purified FSH, LH and/or PRL. A dose-related inhibition of estrogen production from control cells was observed following PRL treatment in which 1 micrograms/ml of PRL inhibited estrogen formation by > 90%. In these same cultures, PRL caused a dose-related increase in progesterone and 20 alpha-dihydroprogesterone secretion. Treatment with purified FSH or LH stimulated estrogen synthesis by 3-10-fold. Concomitant treatment with PRL suppressed the FSH- and LH-induced increases in estrogen production in a dose-dependent manner; 1 micrograms/ml PRL suppressed estrogen production by > 80% during days 2-4 of culture. In these same cultures, PRL did not alter the stimulatory effects of FSH and LH on progesterone and 20 alpha-dihydroprogesterone production. These experiments demonstrate that PRL acts directly on rat granulosa cells in vitro to suppress basal and gonadotropin-induced increases in estrogen production.
Mol Cell Endocrinol 1980 Nov
PMID:Prolactin inhibition of estrogen production by cultured rat granulosa cells. 677 14

Granulosa cells isolated from immature, DES-primed female rats were incubated in medium-199 plus 10% chicken serum with addition of FSH, or testosterone, or both. Cultures were incubated at 37 degree C for 7 days; medium samples were taken daily and analyzed for steroids and plasminogen-activator production. Only cultures containing FSH + testosterone produced significant amounts of both estradiol and progesterone after 2 days of incubation. The rate of estradiol production increased steadily up to the 4th day and then leveled off; the production of progesterone reached a maximum around the 3rd day, and then declined rapidly afterward. FSH alone was able to stimulate plasminogen activator production at the first day. Cultures with FSH + testosterone produced an additional peak of plasminogen activator activity at the 4th day. Plasminogen-activator production is thus not correlated with steroidogenesis in a simple way. We conclude that the granulosa cell require the presence of both FSH and testosterone at the beginning of incubation for normal response. Delayed addition of either hormone, or both, to the culture causes damage to the cells ability to produce normal responses to hormone treatment.
Mol Cell Endocrinol 1981 Jan
PMID:Steroid and plasminogen activator production by cultured rat granulosa cells in response to hormone treatment. 678 52

The direct effect of LH on estrogen secretion by rat granulosa cells was investigated. Ovarian granulosa cells from immature hypophysectomized diethylstilbestrol-treated rats were primed with FSH for 2 days in vitro to induce LH receptors. After the FSH priming, the granulosa cells were washed, and recultured for 4 additional days in media containing aromatase substrate (10(-7) M androstenedione) and purified FSH or LH. After the incubations, estrogen (E), progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-OH-P) in the media were measured by RIA. When granulosa cells from hypophysectomized DES-treated rats were cultured for 6 days with FSH and androstenedione, the production of E, P and 20 alpha-OH-P was stimulated to a maximum of 100-, 200- and 270-fold, respectively, above that of control levels. In contrast, LH did not increase steroidogenesis in these cells. Following 2 days of FSH priming in vitro, however, the cultured granulosa cells exhibited marked increases (400-600%) in E, P and 20 alpha-OH-P production in response to LH treatment over a 4-day incubation period. This stimulatory effect of LH on estrogen and progestin production was dose-related; the minimum and maximum effective doses of LH for steroid production were 3 and 30 ng/ml, respectively, and the ED50 was calculated to be 6 ng/ml of LH. As with LH, FSH also stimulated steroidogenesis in a dose-related manner and the apparent ED50 of FSH on steroidogenesis was 45 ng/ml. To investigate whether LH can also stimulate aromatase activity in granulosa cells primed with FSH in vivo, immature hypophysectomized DES-treated rats were injected for 2 days with FSH after which the granulosa cells were isolated and cultured for 4 days in medium containing 10(-7) M androstenedione and LH or FSH. Both LH and FSH stimulated E, P and 20 alpha-OH-P production, and the maximum steroidogenic responses of LH and FSH were similar to those observed in cultured granulosa cells primed with FSH in vitro. THese results have demonstrated that LH is effective in stimulating both estrogen and progestin secretion in rat granulosa cells pretreated with FSH. This suggests an important role of LH in the direct control of both aromatization and luteinization in the granulosa cell.
Mol Cell Endocrinol 1981 Oct
PMID:LH stimulation of estrogen secretion by cultured rat granulosa cells. 679 41

The rad3 mutant is characterized by a high level of liquid-holding recovery after DEB treatment. The recovery is abolished when the treated cells are postincubated in growth medium, but the effect can be cancelled by suppression of DNA and protein synthesis by specific inhibitors. Alkaline sucrose gradient sedimentation revealed that DEB induces single strand breaks in DNA which are not repaired during post-treatment incubation in growth medium or during LH. Effective repair takes place only when LH is followed by incubation in growth medium. Split-dose treatment applied to test the possible inducibility of repair by LH did not confirm this presumption. In a diploid homozygous for rad3 mutation, DEB induces mitotic inter- and intragenic recombination with very high frequency. Liquid-holding recovery (LHR) was found to be accompanied by an increase in molecular weight of DNA and by a sharp decrease in the frequency of mitotic recombination. The data suggest that recombination events are not involved in LHR pathway.
Mol Gen Genet 1980
PMID:Relation between liquid-holding recovery, DNA repair, and mitotic recombination in the rad3 mutant of Saccharomyces cerevisiae after treatment with diepoxybutane (DEB). 700 23


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