Gene regulation of interleukin-1β, interleukin-1 receptor type I, and plasminogen activator inhibitor-1 and -2 in human granulosa-luteal cells

Piquette, Gary N.; Simón, Carlos; Danasouri, Imam El; Frances, Ana; Polan, Mary Lake

doi:10.1016/s0015-0282(16)57001-0

Cited by 47 publications

(25 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We suggest that periovulatory, gonadotropin-dependent ovarian IL-I1 activity may mediate the maintenance of 20at-HSD in corpora lutea in the absence of pregnancy. This hypothesis is consistent with the dramatic localization of components of the IL-I system in both mouse [3] and human [56] granulosa-luteal cells. In this regard, it is noteworthy that luteinized ovaries secrete large amounts of nitric oxide and that increased nitrite levels are accompanied by decreased progesterone and estradiol production [57].…”

Section: Discussionsupporting

confidence: 87%

Interleukin-1β Inhibits Steroidogenic Bioactivity in Cultured Rat Ovarian Granulosa Cells by Stimulation of Progesterone Degradation and Inhibition of Estrogen Formation1

Donesky

Moura

Tedeschi

et al. 1998

Biology of Reproduction

View full text Add to dashboard Cite

Interleukin (IL)-1beta is a putative regulator of ovulation and perhaps luteal function. In this work, we examine its actions on the steroidogenic cascade of the rat granulosa cell. Whereas treatment of immature granulosa cells with FSH for 72 h produced substantial increments in the accumulation of progesterone, the addition of IL-1beta produced dose-dependent inhibition of this FSH effect. Pulse labeling of cells with [3H]pregnenolone revealed IL-1beta to effect a decrease in the FSH-supported accumulation of [3H]progesterone while enhancing the accumulation of its proximal metabolite, [3H]20alpha-dihydroprogesterone. IL-1beta was without effect on the activity levels of the progesterone-synthesizing enzymes, even though the corresponding transcripts were elevated. The effect of IL-1beta on some progesterone-degrading enzymes was negligible (5alpha-reductase) or modest (3alpha-hydroxysteroid dehydrogenase). In contrast, IL-1beta markedly stimulated both control and FSH-supported 20alpha-hydroxysteroid dehydrogenase activity (4.8- and 3.3-fold, respectively) and transcripts (16.4- and 7.5-fold, respectively). These data demonstrate an IL-1beta-mediated inhibition of gonadotropin-stimulated steroidogenesis via modulation of specific enzymes, and suggest a role for IL-1beta in mediating the observed decline of these bioactive hormones during ovulation and luteolysis.

show abstract

Section: Discussionsupporting

confidence: 87%

Interleukin-1β Inhibits Steroidogenic Bioactivity in Cultured Rat Ovarian Granulosa Cells by Stimulation of Progesterone Degradation and Inhibition of Estrogen Formation1

Donesky

Moura

Tedeschi

et al. 1998

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…Hence a complex intrafollicular cellular communication system comprising IL-13B, its receptors, NOS, and NO is likely to exist at ovulation. While mRNA for IL-1p and the IL-1 receptor type 1 (IL-IRtl) have been found in aspirated granulosa-luteal cells in the human [9,13], rodent mRNA and protein for IL-10 and IL-1Rtl are known to be concentrated in the thecal-interstitial layer before ovulation [10,11]. The mRNA and protein for a constitutive NOS (eNOS) have been localized to preovulatory human granulosa-luteal cells [19], and NOS activity has been shown in luteal phase thecal, granulosa, and CL cells of cynomolgus monkeys [20]; but to our knowledge no localization of iNOS in the ovary has yet been published.…”

Section: Discussionmentioning

confidence: 99%

“…Of particular interest is the cytokine interleukin-lp (IL-1p), which has been shown to be present in the ovary at both the mRNA and protein levels [9,10] and which undergoes an hCG-dependent rise in mRNA just before ovulation [11]. IL-1P enhances ovulation rate in perfused rat ovaries when administered alone, but especially so in the presence of LH [12], and it modulates the activity of ovulatory mediators such as those within the plasminogen activator system [13,14]. Furthermore, local administration of the natural inhibitor of the IL-1 system, the IL-1 receptor antagonist, is known to markedly reduce the hCG-induced ovulation rate of the rat in vivo [15].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Nitric Oxide: Effects on Interleukin-lβ-Enhanced Ovulation Rate, Steroid Hormones, and Ovarian Leukocyte Distribution at Ovulation in the Rat1

Bonello

McKie

Jasper

et al. 1996

Biology of Reproduction

162

View full text Add to dashboard Cite

The ovulatory process resembles an inflammatory reaction with an infiltration of leukocytes, production of inflammatory mediators such as cytokines, and a general edema and hyperemia. Nitric oxide (NO), a potent vasodilator and the main mediator of macrophage tumoricidal and bacteriocidal activities, is known to participate in inflammatory reactions and has been shown to mediate the interleukin-1 beta (IL-1 beta)-directed tissue-remodeling events within the ovary. The regulation by NO of ovulation rate, leukocyte distribution, and steroid release in the rat ovary was investigated through use of a combination of in vivo and in vitro models of ovulation and a competitive inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), of the NO synthase (NOS) enzyme. Subcutaneous L-NAME (1.5 x 10(-4) mol/kg) administration significantly reduced the in vivo ovulation rate of eCG/hCG-primed rats (L-NAME-treated: 10.6 +/- 1.8 [mean +/- SEM] oocytes per ovary [O/O], 11.0 +/- 1.2 rupture sites per ovary [RS/O]; saline-treated: 18.0 +/- 1.8 O/O, 19.4 +/- 1.1 RS/O; p < 0.01) at 20 h post-hCG. These results were reflected in vitro, where addition of L-NAME (3.5 x 10(-5) mol/L) to LH (0.1 microgram/ml)-perfused ovaries decreased ovulation rate from 8.2 +/- 1.6 to 2.7 +/- 1 ovulations per ovary (p < 0.05) and simultaneously decreased nitrite accumulation at the completion of perfusions from 16.5 +/- 1.9 to 4.1 +/- 0.5 nmol/ml (p < 0.001). The addition of L-NAME to LH+IL-1 beta (4 ng/ml)-perfused ovaries decreased ovulation rate from 15.2 +/- 2.4 to 0.8 +/- 0.8 ovulations per ovary (p < 0.001) and simultaneously decreased nitrite accumulation at 22 h from 22.8 +/- 2.2 to 1.9 +/- 0.6 nmol/ml (p < 0.001). Studies analyzing and manipulating perfusion flow rate indicated that the L-NAME effects on ovulation rate are primarily due to a reduction in flow rate resulting from inhibition of NO, which may be a consequence of the known vasoconstrictor effects of NOS inhibitors. The observed reduction of in vivo ovulation rate by NO inhibition at 20 h post-hCG was associated with a significant reduction in thecal MCA149+ neutrophils at 12 h post-hCG, the expected time of ovulation (L-NAME-treated: 98.4 +/- 9.2 cells per thecal area; saline-treated: 211.5 +/- 11.5 cells per thecal area; p < 0.001), while ED1+ monocytes/macrophages underwent similar but nonsignificant changes. Plasma (20 h post-hCG) and perfusate progesterone were not different with L-NAME treatment, while perfusate estradiol levels were markedly reduced upon addition of L-NAME, suggesting a role for NO in ovulation but not in the process of luteinization. In summary, deprivation of NO by use of the competitive inhibitor, L-NAME, led to fewer ovulations, reduced accumulation of nitrite, a decreased neutrophil count in the theca of preovulatory follicles, and reduced estradiol secretion, while progesterone release remained unaffected. The NO pathway may therefore play an important role in the regulation of ovulation and the mediation of IL-1 beta's pro-ovulatory effects. There ar...

show abstract

“…The relationship between PAI-1 levels and cardiovascular risk is not clear [10,11]. Moreover, some studies speculated that overproduction of PAI-1 leads to distortions in the ovarian plasminogenplasmin pathway and anovulation in women with PCOS [12,13]. PAI-1 levels and metabolic parameters that can affect the PAI-1 concentrations in women with PCOS are still under debate.…”

mentioning

confidence: 99%

The Plasminogen Activator System in Young and Lean Women with Polycystic Ovary Syndrome

et al. 2004

View full text Add to dashboard Cite

Abstract. The purpose of the study was to evaluate the plasminogen activator inhibitor-1 (PAI-1) levels and PAI-1 activity in young and lean women with PCOS and to compare with controls matched for age and weight. Thirty two women with PCOS and 25 weight and age-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for hematological and biochemical tests. Fasting insulin, glucose, lipid profile, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone, androstenedione, PAI-1 antigen; PAI-1 activity, insulin sensitivity indices (HOMA and QUICKI) were measured. PAI-1 Ag and activity were significantly higher in PCOS women than healthy control group. PAI-1 levels were directly correlated with BMI, insulin levels and insulin sensitivity indices. PAI-1 activity was also correlated with insulin levels and insulin resistance. As a conclusion PAI-1 Ag levels and activity were increased in lean PCOS women and these were directly correlated with insulin resistance. The finding may contribute to evidence of increase risk of cardiovascular disease and anovulatory infertility in PCOS women. Plasminogen activator inhibitor-1 (PAI-1) is a 52 kD glycoprotein whose main role is in the inhibition of plasmin formation during plasminogen activation and fibrinolysis [9]. The relationship between PAI-1 levels and cardiovascular risk is not clear [10,11]. Moreover, some studies speculated that overproduction of PAI-1 leads to distortions in the ovarian plasminogenplasmin pathway and anovulation in women with PCOS [12,13]. PAI-1 levels and metabolic parameters that can affect the PAI-1 concentrations in women with PCOS are still under debate. Insulin resistance is found in women with PCOS independent of body mass index (BMI) [14]. In diabetic patients, insulin resistance correlated linearly with plasma concentrations of PAI-1 [15,16]. Elevated PAI-1 levels have been demonstrated in some studies of women with PCOS [13,17,18]. Therefore it has been suggested that insulin mediated elevation of PAI-1 may contribute to anovulatory infertility and increased risk of cardiovascular disease those were determined in women with PCOS. However most of these studies included obese or over-weight patient and control groups, so it was not clear from these studies whether the finding of raised PAI-1 levels in women with PCOS was independent of obesity or not. The present study was designed to evaluate PAI-1 levels and activity in young and lean women with PCOS and compare with

show abstract

Gene regulation of interleukin-1β, interleukin-1 receptor type I, and plasminogen activator inhibitor-1 and -2 in human granulosa-luteal cells

Cited by 47 publications

References 22 publications

Interleukin-1β Inhibits Steroidogenic Bioactivity in Cultured Rat Ovarian Granulosa Cells by Stimulation of Progesterone Degradation and Inhibition of Estrogen Formation1

Interleukin-1β Inhibits Steroidogenic Bioactivity in Cultured Rat Ovarian Granulosa Cells by Stimulation of Progesterone Degradation and Inhibition of Estrogen Formation1

Inhibition of Nitric Oxide: Effects on Interleukin-lβ-Enhanced Ovulation Rate, Steroid Hormones, and Ovarian Leukocyte Distribution at Ovulation in the Rat1

The Plasminogen Activator System in Young and Lean Women with Polycystic Ovary Syndrome

Contact Info

Product

Resources

About