Submission Number: BEN-4-1-12

Abstract Number: 238

LEPTIN ATTENUATES FOLLICULAR APOPTOSIS AND ACCELERATES THE ONSET OF PUBERTY IN IMATURE RATS.

B Almog ^1,2, Ronen Gold ^1,2, Ada Dantes ¹, Dalit Barkan ³, Roy Homburg ², JB Lessing ², Nava Nevo ¹, Menahem Rubinstein ³, Arieh Gertler ⁴ and Abraham Amsterdam ¹

Dept of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel ¹
Dept of Obstetrics and Gynecology, LIS Maternity Hospital, Tel-Aviv Medical Center, Tel-Aviv, Israel ²
Dept of Molecular Genetic, Weizmann Institute of Science, Rehovot, Israel ³
Faculty of Agriculture, Hebrew University, Rehovot, Israel ⁴

Abstract:
Human and rat granulosa cells express receptors to leptin which synergies with glucocorticoid hormones in stimulation of ovarian steroidogenesis. To examine whether leptin affects follicular development and maturation, we injected daily recombinant ovine leptin (300ng-10mg /animal) to immature 21 day-old female rats. In non-treated rats puberty was reached at 42-45 days. In Contrast in leptin treated animals puberty was reached at 31-34 days. Ovarian sections revealed hypertrophy of granulosa cells in leptin treated animals. Moreover the number of ovulation was 2-fold higher in the treated animals compared to controls (3-4 ovulation versus 7-8 on the first three estrous cycles). Leptin dramatically reduced incidence of follicular apoptosis measured by TUNEL, evident after 7 days of leptin injection ( 9%-12% of apoptosis in leptin treated group compare to 42%-49% in controls). Maximal protection was achieved at 1-3mg leptin/animal. To reveal whether modulation of death and survival genes are involved in leptin attenuation of follicular apoptosis, we examined the expression of the survival gene Bcl-2 and the death gene Bax in Western blots of ovarian homogenates. There was a constant elevation in Bcl-2 expression during 7-14 days of leptin injection up to 16.3-fold compared to Bcl-2 expression in controls. Bax expression was elevated only 3.4 fold, demonstrating a clear increase in the Bcl-2 /Bax ratio of 4.7 folds. Expression of the tumor suppressor gene P53 and the oncogene Mdm2 did not change significantly. Our data suggest that leptin may be involved in accelerating follicular maturation by attenuating follicular atresia and increasing the ratio of Bcl-2/Bax. Whether leptin could be considered in treatment of amenorrhea and unovulation should be further explored. .

Keywords: leptin, apoptpsis, puberty,Bcl-2, Bax, P53, Mdm2, follicular development and maturation

This abstract is being presented at: 2:00 PM in session:
SESSION 11: APOPTOSIS IN REPRODUCTIVE BIOLOGY