scholarly journals Inhibitory effect of leptin on the rat ovary during the ovulatory process

Reproduction ◽  
2006 ◽  
Vol 132 (5) ◽  
pp. 771-780 ◽  
Author(s):  
A G Ricci ◽  
M P Di Yorio ◽  
A G Faletti

The aims of this study were to investigate the negative action of leptin on some intraovarian ovulatory mediators during the ovulatory process and to assess whether leptin is able to alter the expression of its ovarian receptors. Immature rats primed with gonadotrophins were used to induce ovulation. Serum leptin concentration was diminished 4 h after human chorionic gonadotrophin (hCG) administration, whereas the ovarian expression of leptin receptors, measured by western blot, was increased by the gonadotrophin treatment. Serum progesterone level, ovulation rate and ovarian prostaglandin E (PGE) content were reduced in rats primed with equine chorionic gonadotrophin (eCG)/hCG and treated with acute doses of leptin (five doses of 5 μg each). These inhibitory effects were confirmed by in vitro studies, where the presence of leptin reduced the concentrations of progesterone, PGE and nitrites in the media of both ovarian explants and preovulatory follicle cultures. We also investigated whether these negative effects were mediated by changes in the expression of the ovarian leptin receptors. Since leptin treatment did not alter the expression of ovarian leptin receptor, the inhibitory effect of leptin on the ovulatory process may not be mediated by changes in the expression of its receptors at ovarian level, at least at the concentrations assayed. In summary, the ovulatory process was significantly inhibited in response to an acute treatment with leptin, and this effect may be due, at least in part, to the direct or indirect impairment of some ovarian factors, such as prostaglandins and nitric oxide.

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Eric J Belin de Chantemele ◽  
Anne-Cecile Huby ◽  
P. T Menk ◽  
Weiqin Chen ◽  
Brian Lane ◽  
...  

Obesity is associated with inappropriately high aldosterone levels, which contribute to the development of metabolic and cardiovascular disorders. The origin of these high aldosterone levels is incompletely understood. We recently demonstrated that the adipocyte-derived hormone leptin regulates aldosterone synthase (CYP11B2) expression and stimulates aldosterone release from adrenal zona glomerulosa cells. Recent studies demonstrate that adipocytes express CYP11B2 and secrete aldosterone. However, the mechanisms regulating aldosterone release from adipocytes remain unclear. Likewise, whether visceral (Visc) and subcutaneous (SubQ) adipose tissue contribute to a similar extent to aldosterone production is unknown. We tested the hypothesis that leptin increases adipocyte CYP11B2 expression and aldosterone production and investigated whether Visc and SubQ adipose tissues respond similarly to leptin. Immunostaining of mouse adipose tissue cross-sections and isolated mature adipocytes revealed that Visc and SubQ adipose tissue express leptin receptors. Treatment of mouse freshly isolated mature adipocytes, non-differenciated (stromal fraction) and differentiated adipocytes revealed that leptin dose-dependently increased CYP11B2 expression and aldosterone production in Visc adipose tissue only. Although leptin receptor and CYP11B2 levels were similar in SubQ and Visc adipocytes, SubQ adipocytes were unresponsive to leptin. The physiological relevance of these in vitro data was tested by measuring plasma aldosterone levels in mice deprived of adipose tissue (lipodystrophic mice) treated with leptin. Absence of adipose tissue in lipodystrophic mice blunted leptin-induced increases in aldosterone levels (WT-vehicle: 471±82 vs. WT-Leptin: 1699±396, p<0.05; KO-vehicle: 539±71 vs. KO+leptin: 787±156, NS). The human relevance of these data was determined by reporting that CYP11B2 expression gradually increased with body mass index in human mediastinal and omental fat depots. In summary these data strongly suggest that leptin regulates CYP11B2 levels and aldosterone release in visceral adipose tissue and that leptin-induced, adipocyte-derived aldosterone may contribute to obesity-associated hyperaldosteronism.


2020 ◽  
pp. 1-14
Author(s):  
Daniel Erdwey ◽  
Hendrik Meyer-Lueckel ◽  
Marcella Esteves-Oliveira ◽  
Christian Apel ◽  
Richard Johannes Wierichs

<b><i>Objectives:</i></b> The aim of this in vitro study was to compare the demineralization inhibitory effect of gels/solutions used in combination with either standard or highly fluoridated dentifrices on sound dentin as well as on artificial dentin caries-like lesions. <b><i>Methods:</i></b> Bovine dentin specimens (<i>n</i> = 240) with two different surfaces each (sound [ST] and artificial caries lesion [DT]) were prepared and randomly allocated to twelve groups. Weekly interventions during pH-cycling (28 days, 6 × 120 min demineralization/day) were: the application of gels/solutions containing amine fluoride/sodium fluoride (12,500 ppm F [ppm]; pH = 4.4; AmF); NaF (12,500 ppm; pH = 6.6; NaF1); NaF (12,500 ppm; pH = 6.3; NaF2); silver diamine fluoride (14,200 ppm; pH = 8.7; SDF); acidulated phosphate fluoride (12,500 ppm; pH = 3.8; APF), and no intervention (standard control; S). Furthermore, half of the specimens in each group were brushed (10 s; twice per day) with dentifrice slurries containing either 1,450 ppm (e.g., AmF<sub>1450</sub>) or 5,000 ppm (e.g., AmF<sub>5000</sub>). Differences in integrated mineral loss (ΔΔZ) and lesion depth (ΔLD) were calculated between values before and after pH-cycling using transversal microradiography. <b><i>Results:</i></b> After pH-cycling Ss showed significantly increased ΔZ<sub>DT</sub> and LD<sub>DT</sub> values, indicating further demineralization. In contrast, except for one, all groups including fluoride gels/solutions showed significantly decreased ΔZ<sub>DT</sub> values. Additional use of most fluoride gels/solutions significantly enhanced mineral gain, mainly in the surface area; however, acidic gels/solutions seemed to have negative effects on lesion depths. <b><i>Significance:</i></b> Under the present pH-cycling conditions the highly fluoridated dentifrice significantly reduced caries progression and additional application of nearly all of the fluoride gels/solutions resulted in remineralization. However, there was no difference in the remineralizing capacity of fluoride gels/solutions when used in combination with either standard or highly fluoridated dentifrices.


Endocrinology ◽  
2013 ◽  
Vol 154 (4) ◽  
pp. 1565-1576 ◽  
Author(s):  
Mohsin Syed ◽  
Michael Cozart ◽  
Anessa C. Haney ◽  
Noor Akhter ◽  
Angela K. Odle ◽  
...  

Abstract Deletion of the signaling domain of leptin receptors selectively in somatotropes, with Cre-loxP technology, reduced the percentage of immunolabeled GH cells and serum GH. We hypothesized that the deficit occurred when leptin's postnatal surge failed to stimulate an expansion in the cell population. To learn more about the deficiency in GH cells, we tested their expression of GHRH receptors and GH mRNA and the restorative potential of secretagogue stimulation in vitro. In freshly plated dissociated pituitary cells from control male mice, GHRH alone (0.3 nM) increased the percentage of immunolabeled GH cells from 27 ± 0.05% (vehicle) to 42 ± 1.8% (P &lt; .002) and the secretion of GH 1.8–3×. Deletion mutant pituitary cells showed a 40% reduction in percentages of immunolabeled GH cells (16.7 ± 0.4%), which correlated with a 47% reduction in basal GH levels (50 ng/mL control; 26.7 ng/mL mutants P = .01). A 50% reduction in the percentage of mutant cells expressing GHRH receptors (to 12%) correlated with no or reduced responses to GHRH. Ghrelin alone (10 nM) stimulated more GH cells in mutants (from 16.7–23%). When added with 1–3 nM GHRH, ghrelin restored GH cell percentages and GH secretion to levels similar to those of stimulated controls. Counts of somatotropes labeled for GH mRNA confirmed normal percentages of somatotropes in the population. These discoveries suggest that leptin may optimize somatotrope function by facilitating expression of membrane GHRH receptors and the production or maintenance of GH stores.


1984 ◽  
Vol 62 (9) ◽  
pp. 1166-1169 ◽  
Author(s):  
M. Bernier ◽  
W. Gibb ◽  
R. Collu ◽  
J. R. Ducharme

For this study, purified immature porcine Leydig cells in primary culture were used. After 2 days of culture, the cells were incubated with dexamethasone (5 × 10−9, 1 × 10−7 M) for various periods of time (3–45 h). The media were discarded and treatment was repeated with or without the addition of human chorionic gonadotropin (HCG, 10 mIU/mL) for 3 h. Dexamethasone (10−7 M) decreased testosterone production of HCG-treated cells (up to 40%) in a time-dependent fashion while the lower dose was ineffective. The effect of varying doses (10−8 and 10−6 M) of natural glucocorticoids (corticosterone, cortisol) or synthetic glucocorticoids (triamcinolone, triamcinolone acetonide, betamethasone, dexamethasone) and that of a synthetic progestin (R-5020) on cultured Leydig cells was also studied. After 18 h of preincubation, the various synthetic but not the natural steroids nor R-5020, were able to decrease testosterone production of control and HCG-treated cells by 20–40%. Of a number of other hormonal and nonhormonal substances studied at concentrations of 10−9 – 10−5 M, only lysine8-vasopressin at a concentration of 10−6 M was able to inhibit testosterone production by these cells. These results indicate that dexamethasone and other synthetic glucocorticoids, and to a lesser degree lysine8-vasopressin, may exert a direct inhibitory effect on testosterone production by purified porcine immature Leydig cells in vitro.


2007 ◽  
Vol 292 (5) ◽  
pp. E1456-E1464 ◽  
Author(s):  
Griselda Irusta ◽  
Fernanda Parborell ◽  
Marta Tesone

Our objective was to study the direct action of a GnRH-I agonist, leuprolide acetate (LA), on ovarian steroidogenesis in preovulatory follicles obtained from equine chorionic gonadotropin (eCG)-treated rats. Previously, we have demonstrated an inhibitory effect of LA on steroidogenesis and follicular development. In this study, we tested the hypothesis that gonadotropin-releasing hormone (GnRH) exerts its negative effect on follicular development by inhibiting thecal cytochrome P-450 C17 (P450C17) α-hydroxylase expression and, consequently, androgen synthesis. Studies were carried out in prepubertal female rats injected with either eCG (control) or eCG plus LA (LA) and killed at different time points. Immunohistochemical studies indicated that LA induced steroidogenic acute regulatory protein (StAR) expression mainly in theca cells of preantral and antral follicles. In addition, serum progesterone levels increased significantly ( P < 0.05), whereas those of androsterone decreased ( P < 0.05) after 8 h of LA treatment. This inhibition caused by LA seemed to be a consequence of the decreased expression of follicular P450C17 α-hydroxylase, as demonstrated by Western blot and RT-PCR techniques. In vitro studies using follicles isolated from 48-h-eCG-treated rats and cultured with LA showed a significant ( P < 0.05) inhibition of FSH-induced androsterone follicular content as well as P450C17 α-hydroxylase protein levels, as determined by Western analysis. However, LA increased StAR protein expression in these follicles without significant changes in P450scc enzyme levels. Taking all these findings into account, we suggest that GnRH-I exerts a direct inhibitory action on gonadotropin-induced follicular development by decreasing the temporal expression of the P450C17 enzyme and, consequently, androgen production, thus reducing the supply of estrogens available to developing follicles.


1990 ◽  
Vol 125 (2) ◽  
pp. 287-292 ◽  
Author(s):  
T. Tominaga ◽  
J. Fukata ◽  
Y. Naito ◽  
Y. Nakai ◽  
S. Funakoshi ◽  
...  

ABSTRACT We have examined the mechanism by which corticostatin-I (CS-I) acts to attenuate ACTH-induced steroidogenesis in rat adrenal cells. CS-I inhibited ACTH-induced corticosterone production in a dosedependent manner, without any effects on the basal corticosterone level in adrenal cells. When the cells were stimulated by 100 pg ACTH/ml, the minimum effective concentration of CS-I was 100 ng/ml, and 0.3–1.0 μg CS-I/ml produced a 50% reduction of the stimulated corticosterone production. The inhibitory effect of CS-I on ACTH-stimulated corticosterone production became apparent within 15 min of incubation, and the effect was reversed quickly by the removal of CS-I from the media. CS-I had no effect on angiotensin II-stimulated aldosterone production by adrenal zona glomerulosa cells. CS-I also did not affect cyclic AMP- or forskolin-stimulated corticosterone production. In an in-vitro binding study using 125I-labelled CS-I, CS-I showed considerable specific binding to rat adrenal cells, and the binding competed with ACTH in a dose-dependent manner. These experiments suggest that CS-I competes with ACTH on their binding sites and exerts an inhibitory effect on the adrenal cells. Journal of Endocrinology (1990) 125, 287–292


2016 ◽  
Vol 28 (3) ◽  
pp. 269 ◽  
Author(s):  
L. O'Hara ◽  
N. Forde ◽  
P. Duffy ◽  
F. Randi ◽  
A. K. Kelly ◽  
...  

The aim was to examine the effect of a single intramuscular (i.m.) injection of equine chorionic gonadotrophin (eCG) on Day 3 after oestrus on corpus luteum (CL) development, circulating progesterone and conceptus development in cross-bred beef heifers. In Experiment 1, heifers received: (1) saline, or a single i.m. injection of eCG on Day 3 at (2) 250 IU (3) 500 IU (4) 750 IU or (5) 1000 IU. Administration of eCG resulted in increased luteal tissue area and progesterone and oestradiol concentrations compared with controls. In Experiment 2, heifers received (1) a progesterone-releasing intravaginal device (PRID Delta) from Day 3 to 5 or (2) a PRID Delta from Day 3 to 5 plus a single injection of 750 IU eCG on Day 3. In vitro-produced blastocysts (n = 10 per recipient) were transferred on Day 7 and heifers were slaughtered on Day 14 to assess conceptus development. Administration of eCG reduced the number of short cycles (6.3% vs 31.3%) and increased mean luteal tissue weight (P = 0.02). Insertion of a PRID Delta on Day 3 resulted in an elevation (P < 0.05) in serum progesterone until removal on Day 5. Administration of eCG at the time of PRID Delta insertion resulted in higher progesterone levels (P < 0.05) from Day 10 onwards. Conceptus dimensions were not affected. In conclusion, a single injection of eCG on Day 3 increased CL size and progesterone concentrations and, when given in conjunction with a progesterone-releasing device, appeared to reduce the number of short cycles, presumably due to its luteotrophic nature. The implications of the elevated oestradiol concentrations for embryo quality require further study.


Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Muren Herrid ◽  
Van Ly Nguyen ◽  
Geoff Hinch ◽  
James R McFarlane

There is accumulating evidence that leptin may be directly involved in pre-implantation embryonic development, however, it is unclear whether there is a concentration and stage-dependent regulatory pattern. In this study, the addition of 10 ng/ml human recombinant leptin to the culture medium significantly increased the percentage of two-cell mouse embryos that developed into blastocysts and hatched blastocysts, whereas in the presence of 100 ng/ml leptin, the development rate was significantly inhibited. The total cell numbers in the hatched blastocysts were significantly higher in the presence of 10 ng/ml leptin compared with controls and higher concentrations. The differential sensitivity to leptin was found to vary among embryos at different stages of development. Supplementation of leptin (10 ng/ml) to culture medium at two- to eight-cell stages resulted in a consistent stimulatory effect on embryo development. Most interestingly, the inhibitory effect of high leptin concentration (100 ng/ml) on embryo development was diminished when it was added to the culture medium at the eight-cell stage of development. The concentration-dependent regulation pattern was confirmed using sheep embryos, under similar conditions although sheep embryos appeared to be more sensitive in responding to leptin. Having established the effect of exogenous leptin on embryo development, the expression pattern of leptin and its receptors were also investigated. Leptin mRNA was not detected in mouse two-, four-, eight-cell and blastocyst stage embryos, whereas three isoforms of leptin receptor (Ob-Ra, Ob-Rb and Ob-Re) were identified in these cells, indicating that leptin is likely to modulate embryo development via a paracrine signalling system.


2014 ◽  
Vol 68 (4) ◽  
pp. 245-250 ◽  
Author(s):  
Krystyna Bojarczuk

Adventitious bud cultures were established using vegetative buds from selected clones of poplar (<em>Populus tremula</em> L. x <em>P</em>. <em>alba</em> L.) as initial explants. For multiplication of shoots a modified Murashige and Skoog medium (MS) was used. Aluminium salts (aluminium sulphate and aluminium chloride) were added to the media. It was found that the pH of the medium had no effect on the development of cultures at low concentrations of nutrients (1/2 or 1/4 MS). Low concentrations of aluminium (Al 25mg•dm<sup>-3</sup> supplied as aluminium sulphate, Al 15 mg•dm<sup>-3</sup> as aluminium chloride) had no inhibitory effect on shoot development but decreased regeneration of adventitious roots. High concentrations of aluminium inhibited the development of shoots and roots, especially in a medium at pH 4.5. Microcuttings rooted in the highest percentage and formed the strongest rooting system on 1/4 strength MS medium at pH 4.5. It was found that there was no difference between the rooting of shoots excised from cultures cultivated with or without A1 in this medium at pH 5.5.


PEDIATRICS ◽  
1967 ◽  
Vol 40 (6) ◽  
pp. 993-999
Author(s):  
Barbara Jones

In vitro studies using a mouse liver microsome system failed to demonstrate that menadiol sodium diphosphate, menadione sodium bisulfite, or phytonadione enhanced or inhibited the quantity of ortho-aminophenol glucuronide produced. In vivo studies in young rats with these vitamin K analogues also failed to show an effect on glucuronide conjugation. Based on this data, it is concluded that the hyperbilirubinemia seen in prematures after large doses of water-soluble vitamin K analogues is probably not due to an inhibitory effect of glucuronyl transferase. The evidence suggesting that it may be due in part to hemolysis is briefly reviewed.


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