Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat
Section snippets
Materials and methods
Materials. Human metastin was synthesized as described previously [15]. PMSG and hCG (Teikoku Hormone MFG, Tokyo, Japan), synthetic GnRH peptide (Peptide Institute, Osaka, Japan), GnRH antagonist Cetrorelix (ANASPEC, San José, USA), DNase I, pancreatin, and 17-β estradiol (Sigma–Aldrich, St. Louis, MO), Collagenase A (Roche Diagnostics, IN, USA), Dulbecco’s modified Eagle’s medium (DMEM without phenol red, Invitrogen, CA, USA), and charcoal/dextran-treated fetal calf serum (FCS) (HyClone, UT,
Gonadotropin-releasing activity and ovulation-inducing activity in prepubertal female rats
Subcutaneous administration of metastin (6.7 nmol/body, or ca. 100 nmol/kg) markedly elevated plasma FSH and LH levels compared to each zero-time level and also compared to saline-treated group at each time point in 25-day-old female rats (Figs. 1A and B). The maximal increase was found 2 h after administration. Saline-treatment did not induce any significant changes in these hormone levels. Under the normal physiological conditions, such an explosive LH release is seen in the LH surge that
Discussion
In the present study, we found that s.c. administered metastin dramatically increased plasma FSH and LH levels in three animal models, untreated and PMSG-primed prepubertal female rats, and adult male rats, suggesting that metastin contributes to the release of gonadotropins in both sexes. Increased plasma LH levels were close to the ‘LH-surge level’ ordinary observed in preovulatory female rats. In fact, metastin administration induced ovulation in PMSG-primed rats, which have preovulatory
Acknowledgements
We are grateful to H. Sawada, T. Kokubo, and T. Itoh for providing the synthetic metastin peptide, and S. Usuki, M. Fujino, Y. Fujisawa, K. Okonogi, C. Kitada, and M. Mori for discussions and encouragement.
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