Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The decidualized endometrium during the first trimester of pregnancy synthesizes and secretes a 32-kDa insulin-like growth factor-binding protein (termed hIGFBP-1) at high levels. IGFBP-1 is the major soluble protein product of this tissue and is principally localized to the differentiated endometrial stromal cell, the decidual cell. In the present study long term culture of stromal cells from the nonpregnant endometrium have been employed to elucidate the hormonal requirements for IGFBP-1 production. Immunoreactive IGFBP-1 was undetectable in control cultures. However, inclusion of medroxyprogesterone acetate (MPA) induced rates of 0.35 +/- 0.09 microgram/0.1 mg cell DNA.day (mean +/- SEM; n = 5) after 20-30 days. In these cultures cells exhibited morphological changes consistent with decidual cell differentiation. In all cultures removal of MPA after exposure for 10-16 days, with or without subsequent inclusion of relaxin (RLX), increased production of IGFBP-1 450- to 4600-fold to rates of 150-710 micrograms/0.1 mg cell DNA.day or 26-131 micrograms/10(6) cells.day on days 24-26. The rates tended to be higher with the inclusion of RLX and were sustained in contrast to cultures without RLX, where rates fell by day 30. Individual cultures responded differently to RLX when added from the initiation of culture, with either a response similar to MPA alone or a cyclical change in production, achieving maximal rates of 190-290 micrograms/0.1 mg cell DNA.day. Cultures in which RLX alone induced high IGFBP-1 high production were obtained from endometrium during the progesterone-dominated luteal phase. In cultures exhibiting high rates of immunoreactive IGFBP-1 production, the protein represented their major secretory protein product. This was confirmed by [35S]methionine incorporation and the presence of IGFBP-1 as the predominant protein in serum-free culture medium. The immunoreactive IGFBP-1 isolated from culture medium was found to be identical, by a number of criteria, with IGFBP-1 derived from decidual tissue. These results were consistent with a primary role of progestin exposure, whether in vivo or in vitro, in converting endometrial stromal cells to cells potentially able to exhibit the high rates of IGFBP-1 production typical of the decidualized endometrium of pregnancy.
 ...
PMID:Regulation of insulin-like growth factor-binding protein-1 synthesis and secretion by progestin and relaxin in long term cultures of human endometrial stromal cells. 170 79

Cyclic adenosine 3',5'-monophosphate is known to modulate smooth muscle contractility. Because both relaxin and progesterone have been demonstrated to affect myometrial cyclic adenosine monophosphate activity, we questioned whether the previously observed synergism of these two hormones in inhibiting uterine contractility is mediated via cyclic adenosine monophosphate. Immature rats were treated with estradiol benzoate (n = 7) or a combination of estradiol benzoate and progesterone (n = 7). Uterine horns were isolated, each horn was divided into two segments, and these horn segments were incubated in Ringer-Locke solution, either alone (control) or with 3-isobutyl-1-methylxanthine (MIX) 0.5 mM, MIX 0.5 mM + relaxin 10 ng/ml, or MIX 0.5 mM + relaxin 50 ng/ml. When compared with uterine segments incubated in MIX alone, treatment with MIX + relaxin 50 ng/ml significantly increased cyclic adenosine monophosphate levels in animals treated with estradiol benzoate alone or in combination with progesterone. Relaxin 10 ng/ml was sufficient to significantly elevate mean (+/- SEM) uterine cyclic adenosine monophosphate levels above that of control MIX-treated uteri in animals receiving both estradiol benzoate and progesterone (2.49 +/- 0.39 pm/micrograms deoxyribonucleic acid [DNA] versus 1.08 +/- 0.16 pm/microgram DNA, p less than 0.05) but not in animals receiving estradiol benzoate alone (2.08 +/- 0.32 pm/micrograms DNA versus 1.28 +/- 0.16 pm/micrograms DNA, NS). Compared with treatment with MIX only, MIX + relaxin 10 ng/ml and MIX + relaxin 50 ng/ml produced greater increases in uterine cyclic adenosine monophosphate in the steroid combination group than in the estradiol benzoate controls (144.8% and 233.7% versus 71.7% and 156.6%, respectively). These results suggest that the synergism of relaxin and progesterone in inhibiting uterine contractility may be mediated by intracellular cyclic adenosine monophosphate.
 ...
PMID:Synergistic effect of relaxin and progesterone on cyclic adenosine 3',5'-monophosphate levels in the rat uterus. 246 90

The role of calcium ion mobilization in modulation of secretion of the ovarian protein hormone relaxin by porcine luteal cells was examined by use of a reverse hemolytic plaque assay. In this assay, luteal cells were cocultured in monolayers with protein-A-coupled ovine erythrocytes. In the presence of porcine relaxin antiserum and complement, a zone of hemolysis, a plaque, developed around relaxin-releasing luteal cells. The rate of development of plaques in time-course experiments was used in this study as an index of the rate of relaxin release. Exposure of luteal cell-containing monolayers to the calcium-mobilizing agent A23187 (40 nM to 5 microM) resulted in a dose-related increase in the rate of relaxin-plaque formation. This effect [and the influence of a stimulatory secretagogue, prostaglandin E2 (PGE2; 1 microM)] was suppressed by coculture with Co2+ (5 mM), a calcium channel blocker. These results are consistent with the view that calcium ion redistribution within porcine luteal cells forms a pathway that subserves, at least in part, the rates of basal and stimulated relaxin release in vitro. However, A23187 was equally effective in enhancing the rate of plaque formation when the monolayers were bathed in a low calcium medium (mean +/- SEM, 6.61 +/- 0.92 microM Ca2+), rather than a calcium-replete medium (1.56 +/- 0.09 mM Ca2+). Likewise, neither basal nor PGE2-stimulated (1 microM) relaxin secretion was abrogated by culture of monolayers in low calcium medium. These data suggest that the stimulatory effect of A23187 (and perhaps PGE2) arose predominantly through redistribution of calcium stored within intracellular sites in luteal cells, rather than entrance of calcium into the cell from the extracellular medium. Yet, incompatible with this interpretation, we observed that TMB-8 [8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride; a putative inhibitor of intracellular calcium redistribution] enhanced rather than blocked A23187- or PGE2-stimulated relaxin release. This result is consistent with the possibility that TMB-8 mobilized (rather than blocked) calcium in this cell system or that it acted via calcium-independent mechanisms. We conclude that calcium mobilization has the potential to act as a molecular pathway that transduces secretion of an ovarian peptide hormone, relaxin. However, the exact nature and physiological role(s) of the Ca2+ pathway in the control of relaxin secretion and the interrelationships of this mechanism with other intracellular messengers that may also modulate ovarian peptide secretion remain to be more clearly defined.
 ...
PMID:Regulation of relaxin release from monodispersed porcine luteal cells: effect of calcium ionophore A23187 and calcium channel blockers. 313 4

These studies were designed to determine the tissue source of ovine relaxin and to determine the feasibility of using the pregnant ewe for study of relaxin production and secretion. On Day 4 of gestation, ewes were laparotomized, the nonpregnant uterine horn was ligated, and the ovary not containing the corpus luteum was removed. During a second surgery at Day 45 (n = 8) or 140 (n = 9) of gestation, 10-ml blood samples were drawn from a uterine artery, the ovarian vein, and veins draining the pregnant and nonpregnant uterine horns. Endometrial, placental, and luteal tissues were obtained for immunocytochemistry and extraction. Relaxin was detected by a heterologous porcine radioimmunoassay (RIA) in 3 of 54 serum samples (701.3 +/- 25.4 pg/ml, mean +/- SEM). Relaxin was not detected in crude tissue extracts, but low quantities were detected by RIA following Sephadex G-50 column chromatography of tissue extracts. Total relaxin activity for all tissues was equivalent to 0.57 +/- 0.13 ng of porcine relaxin/g tissue (w.w.). Relaxin was not detected immunocytochemically by light or electron microscopy. These data indicate that low quantities of relaxin are present in tissues and sera of pregnant ewes.
 ...
PMID:Relaxin concentrations in endometrial, placental, and ovarian tissues and in sera from ewes during middle and late pregnancy. 389 Sep 68

Peripheral concentrations of immunoreactive relaxin are undetectable in primates during the nonfertile menstrual cycle, but become measurable during the interval when chorionic gonadotropin (CG) rises in early pregnancy. The objectives of the current study were to determine if exogenous CG, administered in a dosage regimen which invoked patterns and concentrations resembling those of early pregnancy, would induce relaxin secretion in nonpregnant rhesus monkeys, and whether the induction was dependent on the age of the corpus luteum (CL) at the onset of treatment. Female rhesus monkeys received twice-daily i.m. injections of increasing doses of human CG (hCG) for 10 days beginning in the early (n = 4), mid (n = 6) or late (n = 4) luteal phase of the menstrual cycle [5.3 +/- 0.3, 8.3 +/- 0.5, and 12.0 +/- 0.4 days after the midcycle luteinizing hormone (LH) surge, respectively; means +/- SEM]. Whereas immunoreactive relaxin was nondetectable in the luteal phase of posttreatment cycles, detectable levels of relaxin were observed in 2 of 4, 5 of 6, and 3 of 4 monkeys during hCG treatment in the early, mid and late luteal phase, respectively. Although CG treatment rapidly enhance progesterone levels, the appearance of relaxin was deferred; relaxin was first detectable 9.0 +/- 1.0 and 4.7 +/- 1.9 days after the onset of CG treatment at early and late luteal phases. Patterns of relaxin concentrations differed among groups (P less than 0.05, ANOVA; split plot design) and relaxin levels were lowest (P less than 0.01) in monkeys treated during the early luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Induction of relaxin secretion in rhesus monkeys by human chorionic gonadotropin: dependence on the age of the corpus luteum of the menstrual cycle. 651 24

To investigate the control mechanisms for the secretion of relaxin in pregnant rats, the effects of the fetus, placenta, and uterus were studied. Plasma immunoreactive relaxin and progesterone were measured in pregnant rats, from days 8--1 post partum. On day 16 of pregnancy, groups of animals were subjected to removal of the fetuses, conceptuses (fetuses and placentae), or uteri. To determine whether there are extraovarian sources of circulating relaxin, a group of pregnant rats was ovariectomized on day 16. Immunoreactive relaxin was undetectable in the plasma of pregnant rats before day 10, and increased to a mean concentration of 0.52 +/- 0.01 (SEM) ng/ml on day 13. In control animals, immunoreactive relaxin levels remained at about this concentration throughout the remainder of pregnancy and declined rapidly post partum. The pattern of secretion of relaxin in fetectomized animals was similar to that in controls. In contrast, a significant decline in immunoreactive relaxin was seen, within 24 h after surgery, in those animals in which removal of the conceptuses or hysterectomy was performed. In these animals, immunoreactive relaxin was undetectable within 48 h after surgery and remained undetectable throughout the experimental period. In animals that were ovariectomized, immunoreactive relaxin was undetectable 24 h after surgery. Progesterone secretion in animals that had fetectomy or removal of the conceptuses performed was similar to that in controls. These groups showed a significant decline in progesterone on day 17 of pregnancy, and progesterone continued to decline until day 1 post partum. Progesterone in hysterectomized animals declined more abruptly than in either controls or other experimental groups. Ovariectomy resulted in a prompt fall in plasma progesterone. These results indicate that in the rat, the fetus is not needed for the maintenance of relaxin secretion throughout pregnancy, the placenta controls the ovarian secretion of relaxin. The uterus does not exert a tropic effect upon relaxin secretion, no extraovarian sources of circulating relaxin exist in the rat, and there is a divergence between progesterone and relaxin secretion during rat pregnancy.
 ...
PMID:Placental control of ovarian immunoreactive relaxin secretion in the pregnant rat. 725 57

Relaxin immunoactivaity concentrations in the peripheral sera been measured during pregnancy and parturition in rats with a homologous rat relaxin RIA. Relaxin was not detected until day 10 of pregnancy (day 10). Relaxin levels increased markedly over the next 4 days and generally ranged between 50-100 ng/ml from days 14-20. A prepartum surge in relaxin levels, which appeared to be associated with the photoperiod, occurred on day 21 in unanesthetized rats bled via indwelling jugular cannulas. Mean relaxin levels in these animals increased sharply from less than 80 ng/ml on day 20 to approximately 140 ng/ml at 1400 h on day 21 and declined to less than 60 ng/ml during the 12-24 h preceding parturition. The prepartum surge in relaxin immunoactivity may be associated with luteolysis, since there was an accelerated decline in progesterone concentrations concurrent with the prepartum relaxin surg. Rats also experienced a surge in relaxin concentrations during parturition. The mean maximal level of relaxin during parturition was approximately 180 ng/ml. The rate of decline of rat relaxin immunoactivity levels after bilateral ovariectomy on day 21 demonstrated characteristics of a multiexponential curve. The mean clearance t 1/2 from 0-30 min was 22 +/- 3 min (+/- SEM), and the mean t 1/2 from 30-180 min was 56 +/- 7 min (+/0 SEM).
 ...
PMID:Radioimmunoassay of relaxin throughout pregnancy and during parturition in the rat. 739 75

The effect of long-term dietary taurine insufficiency on reproductive function was studied in adult female domestic cats (n = 11). Cats were time-mated during taurine-deficient (6 months) and refed (6 months) states, and the outcome of ovulatory cycles and breeding was analysed. Serum progesterone and relaxin concentrations were evaluated in order to characterize pregnancies, including those resulting in resorption of fetuses, and pseudopregnancies. Increased resorption of fetuses, reduced litter size, and increased incidence of stillborn kittens was observed in queens while on taurine-deficient diets, as well as after refeeding of a taurine-enriched diet. Overall, 30% of the ovulatory cycles resulted in the delivery of kittens, with mean live and stillborn litter sizes of 2.2 +/- 0.4 and 0.8 +/- 0.4 kittens (mean +/- SEM), respectively. The remaining ovulatory cycles resulted either in pregnancies in which fetuses were resorbed (38%), or in pseudopregnancies (32%). Ovulatory cycles resulting in resorbed fetuses were characterized by the appearance of relaxin on day 20 of gestation, but with a subsequent decrease to non-pregnant concentrations by day 25 of gestation. These results suggest that reproductive failure in domestic cats exposed to long-term nutritional taurine deficiency is associated with a postovulatory defect manifest within the first 10 days after implantation, and that this defect is not reversible upon refeeding of a taurine-enriched diet for 6 months.
 ...
PMID:Pregnancy failure in cats associated with long-term dietary taurine insufficiency. 822 62

To investigate the control of relaxin (Rlx) secretion in men, we studied seminal plasma Rlx concentrations after physiologic and supraphysiologic gonadal stimulation. In the first experiment, 14 men with idiopathic hypogonadotropic hypogonadism provided semen samples at various time points before and during therapy with pulsatile GnRH. These data were compared to seminal plasma Rlx values in 5 normal men. In a second experiment, pharmacologic doses of hCG were administered in a fashion similar to that previously shown to have stimulated Rlx secretion from the CL of women. In men with idiopathic hypogonadotropic hypogonadism, no relationship was detected by linear regression analysis between seminal plasma Rlx and testosterone, testicular volume, ejaculate volume, or the appearance of sperm in the ejaculate. Rlx concentrations varied considerably between subjects (6-120 ng/ml) but remained fairly consistent within the same individual over time. Supraphysiologic gonadal stimulation with hCG similarly failed to alter seminal plasma Rlx (n = 5, mean +/- SEM; 48 +/- 9 ng/ml, 42 +/- 7 ng/ml, and 56 +/- 9 ng/ml on Days 1, 3, and 6, respectively; p < 0.05) in normal men despite dramatic increases in serum testosterone (763 +/- 25 ng/dl, 1702 +/- 136 ng/dl, and 1494 +/- 97 ng/dl on Days 1, 3, and 6, respectively; p < 0.05 vs. Day 1). Taken together, these data suggest that Rlx in men is secreted independently from direct gonadotropin control.
 ...
PMID:Relaxin secretion into human semen independent of gonadotropin stimulation. 831 42

The effects of human recombinant relaxin on ovulation and ovarian steroidogenesis were investigated in vitro using a perfused rat ovary model. Ovaries of equine chorionic gonadotrophin (ECG; 20 IU)-primed Sprague-Dawley rats were perfused for 21 h. Ovarian release of oestradiol and progesterone was measured during the perfusion period and the number of ovulations was estimated by counting the released oocytes at termination of the experiment. Non-treated control ovaries did not ovulate whereas addition of ovine luteinizing hormone (LH; 100 ng/ml) resulted in a mean (+/- SEM) number of ovulations of 3.0 +/- 0.8 from all treated ovaries. Relaxin (10 micrograms/ml) induced mean (+/- SEM) number of ovulations at 2.4 +/- 0.2 in all treated ovaries but did not further increase the ovulation rate when combined with LH (mean +/- SEM 3.2 +/- 0.4). All ovulated oocytes in the groups stimulated by LH showed signs of nuclear maturation (germinal vesicle breakdown) when harvested, in contrast to ovulated oocytes in the relaxin group, which were immature (presence of germinal vesicle). Progesterone and oestradiol release was significantly increased in the LH-stimulated groups but not in the group treated only with relaxin, in comparison to the untreated control group. These results demonstrate that relaxin may have a paracrine role within the ovary and may facilitate ovulation, possibly by promoting connective tissue remodelling of the follicle wall.
 ...
PMID:Relaxin induces ovulations in the in-vitro perfused rat ovary. 840 79


1 2 Next >>