Leptin Inhibits Steroid Biosynthesis by Human Granulosa-Lutein Cells

Ghizzoni, Lucia; Barreca, Antonina; Mastorakos, George; Furlini, Mariangela; Vottero, Alessandra; Ferrari, Bruno; Chrousos, Georgios; Bernasconi, S.

doi:10.1055/s-2001-15419

Cited by 65 publications

(39 citation statements)

References 30 publications

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“…In this work, we found that leptin is able to induce a biphasic effect on progesterone production. A direct inhibitory action of leptin on steroid hormone secretion has been demonstrated independently by different authors in the ovary (Spicer & Francisco 1997, Zachow & Magoffin 1997, Agarwal et al 1999, Barkan et al 1999, Zachow et al 1999, Ghizzoni et al 2001, Kikuchi et al 2001 and in other tissues (Tena-Sampere et al 2001, Cameo et al 2003. However, findings of both stimulation and inhibition effect with different levels of leptin in ovarian cells in vitro are in agreement with observations by Ruiz-Cortés et al (2003) who found that the effects of leptin are biphasic with regard to stimulation and inhibition of progesterone synthesis.…”

Section: Ctrlsupporting

confidence: 80%

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Yorio¹,

Bilbao²,

Pustovrh³

et al. 2008

Journal of Endocrinology

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To investigate the expression of leptin receptors (Ob-R) in the rat hypothalamus-pituitary-ovarian axis, immature rats were treated with eCG/hCG and Ob-R expression was evaluated by western blot analysis. The Ob-R expression increased 24 h after eCG administration in all the tissues assayed. In the hypothalamus, these levels immediately decreased to those obtained without treatment. In the pituitary, the Ob-R expression continued to be elevated 48 h after eCG administration, whereas the hCG injection did not modify these levels. Similar results were obtained with the ovarian long isoform. To assess the effect of leptin on its receptors, Ob-R was assessed in hypothalamus, pituitary and ovarian explants cultured in the presence or absence of leptin (0 . 3-500 ng/ml). In the hypothalamus, we found a biphasic effect: the Ob-R expression was either reduced or increased at low or high concentrations of leptin respectively. LH-releasing hormone secretion increased at 1 ng/ml. In the pituitary, Ob-R increased at 10 or 30 ng/ml of leptin for the long and short isoforms respectively. Leptin also induced an increase in LH release at 30 ng/ml. In the ovarian culture, the presence of leptin produced an increase in Ob-R expression at different ranges of concentrations and a dosedependent biphasic effect on the progesterone production. In conclusion, all these results clearly suggest that leptin is able to modulate the expression of its own receptors in the reproductive axis in a differential way. Moreover, the positive or negative effect that leptin exerts on the ovulatory process may be dependent on this regulation.

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Section: Ctrlsupporting

confidence: 80%

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Yorio¹,

Bilbao²,

Pustovrh³

et al. 2008

Journal of Endocrinology

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“…A direct involvement of leptin in ovarian function has been postulated following the demonstration of leptin-receptors in the ovaries of numerous mammalian species (Karlsson et al 1997, Ruiz-Cortés et al 2000, Kikuchi et al 2001. The majorities of studies have suggested that the direct effects of leptin on ovarian cells are inhibitory and can be attributed to attenuation of steroidogenesis (Zachow & Magoffin 1997, Zachow et al 1999, Duggal et al 2000, Spicer et al 2000, Ghizzoni et al 2001, Guo et al 2001. Little is known about the genes targeted by leptin in the ovary.…”

Section: Introductionmentioning

confidence: 99%

Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi

Srivastava¹,

Krishna²

2007

Reproduction

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The aim of the study was to evaluate the seasonal variation in serum leptin levels in a natural population of the female bat, Scotophilus heathi and their relationship to the changes in the body mass, serum insulin level, and ovarian activity. Circulating leptin level varied significantly over the season and correlated positively with the changes in body mass, and circulating insulin and androstenedione (A4) levels. Circulating leptin concentrations showed two peaks; one coincides with the maximum fat accumulation prior to winter dormancy, whereas the second shorter peak coincides with late pregnancy. The in vivo study in S. heathi showed that the increased circulating leptin level during winter dormancy coincides with the decreased expression of ovarian steroidogenic acute regulatory (StAR) protein, and low circulating estradiol (E 2 ) level. At the same time, increased circulating leptin level coincides with increased expression of ovarian insulin receptor and high circulating A4 level. The low circulating leptin level during preovulatory period coincides with the increase in StAR protein but decrease in insulin receptor protein. The in vitro study confirmed the in vivo observations of inhibitory effect of leptin on LH induced StAR expression and E 2 production, whereas the stimulatory effect of leptin (high dose) on LH induced expression of insulin receptor protein and A4 production. However, pharmacological dose of leptin produced inhibitory effect on the expression of insulin receptor protein.The results of the present study thus suggest that high circulating leptin level during winter dormancy promotes adiposity and impairs ovarian activity by suppressing StAR-mediated E 2 production as well as by enhancing insulin receptor-mediated A4 synthesis thereby contributing anovulatory condition of delayed ovulation in S. heathi.

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“…Leptin inhibits IGF-I-stimulated oestradiol secretion from cultured granulosa cells (Spicer & Francisco 1997, Zachow & Magoffin 1997, Zachow et al 1999) and human granulosa lutein cells (Agarwal et al 1999, Greisen et al 2000, Ghizzoni et al 2001, Tsai et al 2002. These findings suggest that leptin has a negative interaction with the intrafollicular IGF system.…”

Section: Introductionmentioning

confidence: 99%

The ovarian expression of mRNAs for aromatase, IGF-I receptor, IGF-binding protein-2, -4 and -5, leptin and leptin receptor in cycling ewes after three days of leptin infusion

Muñoz-Gutiérrez¹,

Findlay²,

Adam³

et al. 2005

Reproduction

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An experiment was carried out to determine the pattern of follicular expression of mRNAs for aromatase, IGF-I receptor (IGF-IR), IGF-binding protein (IGFBP)-2, -4 and -5, leptin and the long form of the leptin receptor (Ob-Rb) in ten ewes infused with human recombinant leptin (n 5 5; 1 mg/h) or saline (n 5 5) for 72 h in the luteal phase of the oestrous cycle. At the end of infusion a follicular phase was induced with a luteolytic dose of a prostaglandin F2a analogue and the ovaries were collected 32 h later. One ovary from each ewe was serially sectioned at 10 mm using a cryostat at 220 8C. All follicles >1 mm in diameter were counted and probed with specific oligoprobes for aromatase, IGF-IR and IGFBP-2, -4 and -5 and specific riboprobes for leptin and Ob-Rb. Leptin mRNA was detected in theca and granulosa cells and Ob-Rb mRNA was detected only in granulosa cells, of some, but not all antral follicles. Leptin doubled the number of follicles with a diameter $3.5 mm (1.0 6 0.36 (S.E.M.) vs 2.4 6 0.24; control vs leptin; P < 0.02) but had no effect on the number of $1 < 3.5 mm follicles. Leptin had no effect on the number of follicles expressing aromatase mRNA but it decreased significantly the number of follicles expressing mRNA for IGF-IR (10.7 6 0.79 vs 7.4 6 0.81; control vs leptin; P < 0.05), IGFBP-2 (10.0 6 0.82 vs 5.2 6 0.87; control vs leptin; P < 0.05) and IGFBP-5 (5.2 6 1.60 vs 1.2 6 0.30; control vs leptin; P < 0.05). Leptin increased the diameter of IGFBP-2 mRNA-positive follicles (1.5 6 0.15 vs 2.2 6 0.31 mm; control vs leptin; P < 0.05) and increased follicular mRNA expression for IGFBP-2 (0.30 6 0.021 vs 0.39 6 0.027 arbitrary units; control vs leptin; P < 0.05) and IGFBP-5 (0.46 6 0.019 vs 0.25 6 0.053 arbitary units; control vs leptin; P < 0.05). The mRNA for IGFBP-4 was detected in the theca of only two follicles from the control group. Leptin increased the number of follicles expressing Ob-Rb mRNA (0.25 6 0.25 vs 1.40 6 1.17; control vs leptin; P < 0.05) but had no effect on the number expressing leptin mRNA. Leptin decreased plasma concentrations of oestradiol (P < 0.05) and increased concentrations of FSH (P < 0.001) and insulin (P < 0.001), with no effect on glucose concentrations. These data show that: (i) ovine granulosa cells express mRNA for Ob-Rb and leptin and (ii) leptin increased the number of follicles $ 3.5 mm. Furthermore, the data suggest that suppression of oestradiol production by leptin is not mediated by inhibition of aromatase gene expression. Finally, the data indicate that the action of leptin in ovarian follicles is mediated by the IGF system, because leptin increased mRNA expression of IGFBP-2 and -5. Leptin also decreased the number of follicles expressing IGF-IR and IGFBP-2 and -5. We suggest that these actions of leptin on the IGF system decrease the bioavailability of IGF-I, resulting in decreased oestradiol production.

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Leptin Inhibits Steroid Biosynthesis by Human Granulosa-Lutein Cells

Cited by 65 publications

References 30 publications

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Leptin modulates the expression of its receptors in the hypothalamic–pituitary–ovarian axis in a differential way

Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi

The ovarian expression of mRNAs for aromatase, IGF-I receptor, IGF-binding protein-2, -4 and -5, leptin and leptin receptor in cycling ewes after three days of leptin infusion

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