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Direct in vivo effects of leptin on ovarian steroidogenesis in sheep

¹ Division of Obstetrics and Gynaecology, School of Human Development, Queen’s Medical Centre, Nottingham NG7 2UH, UK, ² Facultad de Medicina Veterinaria, Universidad Nacional Autonoma de Mexico, Mexico DF 04510, Mexico, ³ Department of Veterinary Basic Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, UK, ⁴ Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, UK and ⁵ Division of Agricultural and Environmental Sciences, School of Biosciences, University of Nottingham, Sutton Bonington LE12 5RD, UK

Correspondence should be addressed to N R Kendall who is now at Division of Animal Physiology, School of Biosciences, University of Nottingham, Sutton Bonington LE12 5RD, UK; Email: Nigel.Kendall{at}Nottingham.ac.uk

Leptin, the metabolic fat hormone, has been shown to have effects on reproduction in mice and to modulate steroid production by cultured ovarian somatic cells in a number of species. However, a direct role of leptin on normal ovarian function in vivo has not been shown. In this paper the effect of passive immunisation against leptin (experiment 1; 20 ml antiserum or non-immune plasma i.v.; n = 6/treatment) and direct ovarian infusion of leptin (experiment 2; 0, 2 or 20 µg recombinant ovine leptin; n = 4/treatment) during the early follicular phase was investigated in sheep with ovarian autotransplants, which allow recovery of ovarian venous blood and regular non-invasive scanning of the ovary.

Passive immunisation against leptin resulted in an acute increase (P < 0.05) in ovarian oestradiol secretion but had no effect on gonadotrophin concentrations, ovulation or subsequent luteal function. Conversely, direct ovarian arterial infusion of the low dose of leptin resulted in an acute decline (P < 0.05) in ovarian oestradiol secretion whereas the high dose, which resulted in supra-physiological leptin concentrations, had no effect on oestradiol production compared with the controls. Neither dose of leptin had any effect on gonadotrophin concentrations or ovulation but both doses resulted in an increase (P < 0.05) in progesterone concentrations over the subsequent luteal phase.

In conclusion, together these data provide strong in vivo evidence that leptin can modulate ovarian steroidogenesis directly and acutely in ruminants and suggest that leptin is an alternate regulatory system whereby nutritional status can regulate reproductive activity.

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