ALPHA-DIFLUOROMETHYLORNITHINE MODIFIES GONADOTROPIN-RELEASING-HORMONERELEASE AND FOLLICLE-STIMULATING-HORMONE SECRETION IN THE IMMATURE FEMALE RAT

Polyamines play an essential role in tissue growth and differentiation , in body weight increment, in brain organization, and in the molecula r mechanisms of hormonal action, intracellular signaling, and cell-to- cell communication, In a previous study, inhibition of their synthesis by alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during development in female rat s, was followed by prolonged high follicle-stimulating hormone (FSH) s erum lever and a delayed puberty onset, Those changes were relatively independent of body mass and did not impair posterior fertility, The p resent work studies the mechanisms and site of action of polyamine par ticipation in FSH secretion during development, DFMO was injected in f emale rats between Days 1 and 9 on alternate days, At 10 days of age, hypothalami from control and DFMO rats were perifused in vitro, and ba sal and potassium-induced gonadotropin-releasing hormone (GnRH) releas e were measured, The response to membrane depolarization was altered i n DFMO hypothalami. Increased GnRH release in response to a low K+ con centration was evidenced, Adenohypophyses of the same treated prepuber tal rats were perifused in vitro and the response to GnRH purses was c hecked. In DFMO-treated rats, higher FSH release was observed, with no changes in LH or PRL secretion. Finally, pituitary GnRH receptor numb er in adenohypophyseal membranes from treated and control groups was q uantified, A significant reduction in specific binding was evident in hypophyses from DFMO-treated rats when compared with binding in the co ntrol group, In summary, DFMO treatment in a critical developmental pe riod in the female rat impacts the immature GnRH neuronal network and immature gonadotropes, A delay in maturation is evidenced by a higher sensitivity to secretagogs in both pituitary glands and hypothalamic e xplants, These events could explain the prolonged high FSH serum fever s and delayed puberty onset seen in this experimental model.