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

Abstract

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.

Action of IGF-I on Expression of the Long Form of the Leptin Receptor (ObRb) in the Prepubertal Period and Throughout the Estrous Cycle in the Mature Pig Ovary

“…More recently, Duggal et al [5] reported that the gene expression of ovarian leptin receptors for both OB-RB and OB-RA vary throughout the estrous cycle in response to the changing environment in the ovary. In our previously published data [2], we clearly showed that IGF-I modulates the action of leptin in prepubertal animals. Moreover, we showed that IGF-I has stimulatory action on leptin expression.…”

“…We showed that growth hormone (GH) and insulinlike growth factor (IGF-I) modulate the action of leptin on steroid secretion by ovarian follicles and the stimulatory action of IGF-I on leptin receptor expression in prepubertal animals [2]. Moreover, leptin has maturation-dependent action on GHand IGF-I-stimulated follicular steroidogenesis.…”

Resistin is a survival factor for porcine ovarian follicular cells

“…This difference is probably due to the animal model used. Other adipokines, such as adiponectin and leptin, were earlier shown to inhibit ovarian apoptosis in different species, including pigs (Gregoraszczuk et al 2006, Sirotkin et al 2012, chickens (Sirotkin & Grossmann 2007), humans (Sirotkin et al 2008), rats (Almog et al 2001), mice (Richards et al 2012) and bats (Srivastava & Krishna 2011).…”

“…The study of the molecular mechanisms that regulate ovarian cell death is important for understanding normal development and a variety of diseases of the ovary. It is a wellknown fact that other adipokines, such as leptin, inhibit apoptosis in cultured chicken ovarian cells (Sirotkin & Grossmann 2007), immature rats (Almog et al 2001) and porcine prepubertal ovarian cells (Gregoraszczuk et al 2006). However, the effect of resistin on ovarian cell apoptosis is still unknown.…”

Supraphysiological leptin levels shift the profile of steroidogenesis in porcine ovarian follicles toward progesterone and testosterone secretion through increased expressions of CYP11A1 and 17β-HSD: a tissue culture approach

“…Later Gregoraszczuk et al (2004) demonstrated that leptin at a dose matching that in follicular fluid had no effect on basal testosterone and estradiol (E 2 ) secretions in small and medium ovarian follicles, whereas in large preovulatory follicles decreased E 2 secretions were observed concomitant with an increase in P 4 secretion. On the other hand, leptin at all concentrations (2, 20, and 200 ng/ml) increased E 2 secretion and significantly diminished caspase-3 activity in ovarian follicles collected from prepubertal pigs (Gregoraszczuk et al 2006). Sirotkin & Meszarosová (2010) noted an increase in P 4 secretion by porcine granulosa cells after the addition of 1 and 10 ng/ml leptin but observed no effect at a dose of 100 ng/ml.…”