Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats

Almog, Benny; Gold, Richard M.; Tajima, Kimihisa; Dantes, Ada; Salim, Kamran; Rubinstein, Menachem; Barkan, Dalit; Homburg, Roy; Lessing, Joseph B.; Nevo, Nava; Gertler, Arieh; Amsterdam, Abraham

doi:10.1016/s0303-7207(01)00543-3

Cited by 110 publications

(75 citation statements)

References 57 publications

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“…Our results are in agreement with data of Almog et al (2001), who demonstrated higher expression of Bcl-2 and an increase in the Bcl-2/Bax ratio in ovarian homogenates of 21-day-old female rats after leptin injection. Also, reduced granulosa cell apoptosis and decreased follicular atresia were observed in these animals.…”

Section: Discussionsupporting

confidence: 93%

“…Steroid secretion (progesterone and oestradiol) was measured in culture media. Moreover, taking into consideration the data of Almog et al (2001) who, by injecting recombinant leptin to immature rats daily, have suggested that leptin may be involved in accelerating follicular maturation by attenuating follicular atresia, we measured caspase-3 activity in the cells.…”

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confidence: 99%

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Gh and igf-i increase leptin receptor expression in prepubertal pig ovaries: The role of leptin in steroid secretion and cell apoptosis

Gregoraszczuk

Rak

Wójtowicz

et al. 2006

Acta Veterinaria Hungarica

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Leptin (L) is recognised as an important regulator of puberty and a factor which controls reproduction. Whole pig ovarian follicles were incubated with different doses of leptin (2, 20 and 200 ng/ml) added alone or in combination with 100 ng/ml of GH or 50 ng/ml of IGF-I. The expression of the functional long form leptin receptor (Ob-R b ) mRNA was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in follicular cells cultured with GH or IGF-I. Both GH and IGF-I increased leptin receptor expression in prepubertal pig ovaries. In separate experiments, the action of leptin on ovarian follicular steroidogenesis and cell apoptosis was examined. After 24 h of incubation with leptin alone or in combination with GH or IGF-I, oestradiol (E2) levels were determined in the culture medium while follicular tissue was used for the estimation of caspase-3 activity. Leptin increased E2 secretion and significantly diminished caspase-3 activity at all doses used. Both GH and IGF-I stimulated oestradiol secretion and decreased caspase-3 activity. No differences were demonstrable in oestradiol secretion and caspase-3 activity between cells treated with GH plus leptin and GH alone or cells treated with IGF-I plus leptin as compared to cultures treated with GH or IGF-I alone. However, GH diminished leptin-stimulated oestradiol secretion while IGF-I was without effect on it. Both GH and IGF-I reversed the anti-apoptotic action of leptin. In conclusion, we infer that (1) leptin directly affects ovarian function in prepubertal animals by its action on oestradiol secretion and cell apoptosis, (2) GH and IGF-I modulate the action of leptin, and (3) at least in part, the direct effect of GH/IGF-I on leptin production is due to an action on leptin receptor expression.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Gh and igf-i increase leptin receptor expression in prepubertal pig ovaries: The role of leptin in steroid secretion and cell apoptosis

Gregoraszczuk

Rak

Wójtowicz

et al. 2006

Acta Veterinaria Hungarica

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“…Since mRNA for leptin receptor has been detected in ovarian tissue, many studies have demonstrated that leptin may have direct effects on the ovarian function. However, most of these studies are contradictory, since both stimulatory and inhibitory actions on the ovarian function have been described (Ahima et al 1997, Zachow & Magoffin 1997, Clément et al 1998, Strobel et al 1998, Agarwal et al 1999, Barkan et al 1999, Brannian et al 1999, Zachow et al 1999, Duggal et al 2000, 2002a, Almog et al 2001. Recently, we have demonstrated that leptin may be regulating the ovulatory process, as when the levels of this protein are low there is a positive relationship between leptin and the ovarian function (Roman et al 2005), while when these levels are high, there is a negative relationship between them (Ricci et al 2006).…”

Section: Discussionmentioning

confidence: 97%

“…Leptin is able to produce both stimulating (Ahima et al 1997, Clément et al 1998, Strobel et al 1998, Almog et al 2001, Barkan et al 2005) and inhibitory (Zachow & Magoffin 1997, Agarwal et al 1999, Barkan et al 1999, Brannian et al 1999, Zachow et al 1999, Duggal et al 2000, 2002a effects on the ovarian function. In previous studies, we found that ovulation is significantly inhibited by an acute treatment with leptin (Ricci et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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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“…27 In addition, daily injections of recombinant leptin to 21-day-old female rats caused a significant increase in Bcl-2 expression and Bcl-2/Bax ratio in granulosa cells. 28 Evidence of leptin-induced white adipose tissue apoptosis 17,18 suggests that leptin is not acting to increase the Bcl-2/Bax ratio in these tissues but no data are available in the literature to support this or that otherwise detail the effect of leptin on this process in adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue cellularity and apoptosis after intracerebroventricular injections of leptin and 21 days of recovery in rats

et al. 2003

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OBJECTIVE:To determine the effect of leptin and post-treatment recovery on adipose tissue cellularity and apoptosis. In addition, to investigate whether Bcl-2 and/or Bax is involved in the mechanism of leptin-induced adipose tissue apoptosis. DESIGN: A total of 24 adult male Sprague-Dawley rats were injected i.c.v. with either 10 mg mouse leptin or 10 ml vehicle once per day for 4 days. At 24 h after the last injection, one group was killed while the other was monitored for 21 days. MEASUREMENTS: DNA fragmentation and Bcl-2 and Bax protein levels were determined in inguinal (ING), epididymal (EPI) and retroperitoneal (RP) white adipose tissues and the interscapular brown adipose tissue (BAT). Cellularity was determined in ING and EPI. RESULTS: Leptin significantly reduced the masses of all white fat pads [RP>ING>EPI] but not BAT. Cell volume was significantly reduced in EPI and ING. Only ING had a significantly reduced cell number from leptin treatment plus exhibited apoptosis by increased DNA fragmentation and DNA laddering, and upregulation of pro-apoptosis Bax protein. The other fat pads exhibited a general trend to increase the Bcl-2/Bax ratio. Recovery allowed for normalization of white fat pad mass, cell number and cell volume; however, BAT mass increased 42% over control. After recovery, apoptosis was not detected, Bcl-2 protein had increased in ING, and the Bcl-2/Bax ratio had risen overall. CONCLUSIONS: Central administration of mouse leptin in the rat targets white fat depots individually to reduce mass by a reduction in cell volume plus adipocyte deletion in, at least, the ING fat pad by Bax-mediated apoptosis. Even after a dramatic loss in adipose tissue mass and change in cellularity, the rat demonstrates a resilient return to control levels together with an increase in factors that prevent adipocyte loss.

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Leptin attenuates follicular apoptosis and accelerates the onset of puberty in immature rats

Cited by 110 publications

References 57 publications

Gh and igf-i increase leptin receptor expression in prepubertal pig ovaries: The role of leptin in steroid secretion and cell apoptosis

Gh and igf-i increase leptin receptor expression in prepubertal pig ovaries: The role of leptin in steroid secretion and cell apoptosis

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

Adipose tissue cellularity and apoptosis after intracerebroventricular injections of leptin and 21 days of recovery in rats

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