scholarly journals Chemerin, a Novel Regulator of Follicular Steroidogenesis and Its Potential Involvement in Polycystic Ovarian Syndrome

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5600-5611 ◽  
Author(s):  
Qi Wang ◽  
Ji Young Kim ◽  
Kai Xue ◽  
Jia-yin Liu ◽  
Arthur Leader ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Polycystic Ovarian Syndrome ◽  
Regulatory Protein ◽  
Hydroxysteroid Dehydrogenase ◽  
Negative Regulator ◽  
Estradiol Secretion ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory ◽  
Ovarian Syndrome

Abstract Polycystic ovarian syndrome (PCOS) is a heterogeneous syndrome associated with follicle growth arrest, minimal granulosa cell proliferation, dysregulated sex hormone profile, hyperthecosis, and insulin resistance. Using a 5α-dihydrotestosterone (DHT)-induced rat model that recapitulates the reproductive and metabolic phenotypes of human PCOS, we have examined the steroidogenic capability of granulosa cells from DHT-treated rats. Gene expression of several key steroidogenic enzymes including p450 side-chain cleavage enzyme (p450scc), aromatase, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenase-17β, and hydroxysteroid dehydrogenase-3β were markedly lower in DHT-treated rats than the controls, although the responsiveness of their granulosa cells to FSH was higher. Expression of the adipokine chemerin and its receptor, chemokine receptor-like 1, was evident in control and DHT-treated rats, with significantly higher ovarian mRNA abundances and protein contents of chemerin and its receptor. Recombinant chemerin decreases basal estradiol secretion in granulosa cells from DHT-treated rats. When the inhibitory role of chemerin on steroidogenesis was further examined in vitro, chemerin suppressed FSH-induced progesterone and estradiol secretion in cultured preantral follicles and granulosa cells. Chemerin also inhibits FSH-induced aromatase and p450scc expression in granulosa cells. Overexpression of nuclear receptors NR5a1 and NR5a2 promotes p450scc and aromatase expression, respectively, which is suppressed by chemerin. These findings suggest that chemerin is a novel negative regulator of FSH-induced follicular steroidogenesis and may contribute to the pathogenesis of PCOS.

scholarly journals Insulin and Insulin-Like Growth Factor Stimulation of Vascular Endothelial Growth Factor Production by Luteinized Granulosa Cells: Comparison between Polycystic Ovarian Syndrome (PCOS) and Non-PCOS Women

2007 ◽  
Vol 92 (7) ◽  
pp. 2726-2733 ◽  
Author(s):  
Meghan B. Stanek ◽  
Sherri M. Borman ◽  
Theodore A. Molskness ◽  
Janine M. Larson ◽  
Richard L. Stouffer ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Granulosa Cells ◽  
Polycystic Ovarian Syndrome ◽  
Culture Media ◽  
Vascular Endothelial ◽  
Vitro Fertilization ◽  
Endothelial Growth Factor ◽  
Ovarian Syndrome

Abstract Context: Vascular endothelial growth factor A (VEGF-A) is a potent cytokine that promotes angiogenesis and vascular permeability. After controlled ovarian stimulation (COS) for in vitro fertilization (IVF), excessive VEGF-A production can occur, particularly in women with polycystic ovarian syndrome (PCOS); however, it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women. Objective: The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells (LGCs) from women with and without PCOS. Design and Setting: A prospective comparative experimental study was conducted at an institutional practice. Patients: Patients included six PCOS and six non-PCOS women undergoing COS and IVF. Interventions: Interventions included COS for IVF. Main Outcome Measures: VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin, IGF-I, and IGF-II in the presence and absence of LH. Results: In both study groups, exposure to LH alone did not alter VEGF-A levels. However, insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure, whereas PCOS cells were more sensitive to insulin. Although an increase in DNA content (P < 0.05) was noted in cultures of PCOS cells, progesterone levels were lower compared with non-PCOS LGCs. Conclusion: Insulin and IGFs promote VEGF-A production in LGCs, but the response patterns are different when cells from PCOS and non-PCOS women are compared.

In obese mice, exercise training increases 11β-HSD1 expression, contributing to glucocorticoid activation and suppression of pulmonary inflammation

2017 ◽  
Vol 123 (4) ◽  
pp. 717-727 ◽  
Author(s):  
Shu-Fang Du ◽  
Qing Yu ◽  
Kai Chuan ◽  
Chang-Lin Ye ◽  
Ze-Jia He ◽  
...  
Keyword(s):  
Exercise Training ◽  
Pulmonary Inflammation ◽  
Regulatory Protein ◽  
Hydroxysteroid Dehydrogenase ◽  
Mouse Lung ◽  
Obese Mice ◽  
Chain Cleavage ◽  
Anti Inflammatory ◽  
Steroidogenic Acute Regulatory

Exercise training is advocated for treating chronic inflammation and obesity-related metabolic syndromes. Glucocorticoids (GCs), the anti-inflammatory hormones, are synthesized or metabolized in extra-adrenal organs. This study aims to examine whether exercise training affects obesity-associated pulmonary inflammation by regulating local GC synthesis or metabolism. We found that sedentary obese ( ob/ob) mice exhibited increased levels of interleukin (IL)-1β, IL-18, monocyte chemotactic protein (MCP)-1, and leukocyte infiltration in lung tissues compared with lean mice, which was alleviated by 6 wk of exercise training. Pulmonary corticosterone levels were decreased in ob/ob mice. Exercise training increased pulmonary corticosterone levels in both lean and ob/ob mice. Pulmonary corticosterone levels were negatively correlated with IL-1β, IL-18, and MCP-1. Immunohistochemical staining of the adult mouse lung sections revealed positive immunoreactivities for the steroidogenic acute regulatory protein, the cholesterol side-chain cleavage enzyme (CYP11A1), the steroid 21-hydroxylase (CYP21), 3β-hydroxysteroid dehydrogenase (3β-HSD), and type 1 and type 2 11β-hydroxysteroid dehydrogenase (11β-HSD) but not for 11β-hydroxylase (CYP11B1). Exercise training significantly increased pulmonary 11β-HSD1 expression in both lean and ob/ob mice. In contrast, exercise training per se had no effect on pulmonary 11β-HSD2 expression, although pulmonary 11β-HSD2 levels in ob/ob mice were significantly higher than in lean mice. RU486, a glucocorticoid receptor antagonist, blocked the anti-inflammatory effects of exercise training in lung tissues of obese mice and increased inflammatory cytokines in lean exercised mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local GC activation and suppression of pulmonary inflammation in obese mice. NEW & NOTEWORTHY Treadmill training leads to a significant increase in pulmonary corticosterone levels in ob/ob mice, which is in parallel with the favorable effects of exercise on obesity-associated pulmonary inflammation. Exercise training increases pulmonary 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression but has no significant effect on 11β-HSD2 expression in both lean and ob/ob mice. These findings indicate that exercise training increases pulmonary expression of 11β-HSD1, thus contributing to local glucocorticoid activation and suppression of pulmonary inflammation in obese mice.

scholarly journals Adiponectin is secreted by theca layer cells isolated from chicken ovarian follicles

Reproduction ◽  
2020 ◽  
Vol 159 (3) ◽  
pp. 275-288 ◽  
Author(s):  
Jill A Hadley ◽  
Olga Ocón-Grove ◽  
Ramesh Ramachandran
Keyword(s):  
Granulosa Cells ◽  
Energy Homeostasis ◽  
Glucose Utilization ◽  
Protein Gene ◽  
Regulatory Protein ◽  
Altered Expression ◽  
Steroidogenic Acute Regulatory ◽  
Chicken Ovary ◽  
Serum Free Conditions

Adiponectin, an adipokine hormone, influences glucose utilization, insulin sensitivity and energy homeostasis by signaling through two distinct receptors, ADIPOR1 and ADIPOR2. We previously reported that adiponectin and its receptors are expressed in several organs, including testes in chicken. We report herein that adiponectin gene is expressed exclusively in theca layer while ADIPOR1 and ADIPOR2 genes are expressed in granulosa and theca layers of all preovulatory and prehierarchical follicles of the chicken ovary. Estradiol and/or progesterone treatment of sexually immature chickens significantly altered expression of adiponectin and ADIPOR1 in the ovary. Using anti-chicken adiponectin-, ADIPOR1-, or ADIPOR2- antibodies, adiponectin-immunoreactive (ir) cells were found exclusively in the theca layer, and ADIPOR1-ir and ADIPOR2-ir cells were found both in theca and granulosa layers. Theca layer cells dispersed from preovulatory and prehierarchical follicles were found to synthesize and secrete a 720 kDa heavy molecular weight (HMW) isoform of adiponectin in vitro. Recombinant chicken adiponectin (rcADN) expressed in eukaryotic cells under serum-free conditions comprised primarily of the HMW isoform. Treatment of granulosa cells dispersed from 9 to 12 mm preovulatory follicle and 6 to 8 mm prehierarchical follicle with rcADN or an adiponectin receptor agonist, adipoRon, increased pERK and pACC abundance. In addition, both rcADN and adipoRon were found to significantly decrease the expression of steroidogenic acute regulatory protein gene expression in granulosa cells of preovulatory and prehierarchical follicles. In conclusion, adiponectin secreted by theca cell layer is identical in mass to circulating adiponectin. Systemic and/or theca-derived adiponectin is likely to affect proliferation, metabolism, and steroidogenesis of ovarian follicular cells.

156. EFFECTS OF ALBENDAZOLE ON OVARIAN OESTROGEN SYNTHESIS IN THE RAT

2009 ◽  
Vol 21 (9) ◽  
pp. 74
Author(s):  
I. S. Zulkafli ◽  
P. J. Mark ◽  
G. B. Martin ◽  
B. J. Waddell
Keyword(s):  
Mating Behaviour ◽  
Regulatory Protein ◽  
Reproductive Function ◽  
Hydroxysteroid Dehydrogenase ◽  
Side Chain ◽  
Chain Cleavage ◽  
Rat Ovary ◽  
Steroidogenic Acute Regulatory ◽  
Ovarian Follicular Fluid ◽  
Steroidogenic Genes

Albendazole is a drug commonly used for treatment of helminth infestation in human and livestock populations. Recent studies show that albendazole reduces ovarian follicular fluid oestrogen levels in sheep1, but the mechanism involved is unknown. The aims of this study were to determine whether albendazole exerts similar effects on ovarian oestrogen levels in the rat, and to assess the effects of albendazole on expression of key steroidogenic genes in the rat ovary. Oestrus cycles were continuously monitored in Wistar rats by vaginal smears. Commencing at proestrus, albendazole was administered for 12 days in drinking water (approximate dose 15 mg/kg/day). Plasma and whole ovaries were collected on the fourth proestrus (1500–1600h). A second group of rats were treated similarly except that pseudopregnancy (PSP) was induced by mating with a vasectomised male at the second proestrus. Plasma and the non-luteal ovary were collected on day 8 of PSP. Oestradiol was extracted from plasma and ovaries with ethyl acetate and concentrations measured by a chemiluminescent assay. Expression of steroidogenic acute regulatory protein (StAR), P450 side chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), aromatase and 20α-hydroxysteroid dehydrogenase (20α-HSD) mRNAs were measured by RT-PCR. Oestrus cyclicity, ovarian weight and mating behaviour were all unaffected by albendazole in cycling and PSP rats, although as expected levels of oestradiol were lower in PSP. In ovaries of cycling rats albendazole did not affect oestradiol concentrations but reduced ovarian P450scc mRNA expression (by 65%; P=0.024) and there was a trend for an increase in 3β-HSD (P=0.09) and aromatase expression (P=0.12). Expression of the other steroidogenic genes was unaffected and no changes in gene expression were observed in PSP rats. In conclusion, albendazole treatment reduced ovarian P450scc in cycling rats but did not inhibit ovarian oestradiol synthesis or reproductive function.

Sign in / Sign up

Export Citation Format

Share Document