Endocrine Abstracts

GLP-1 is a gut hormones with insulinotropic effects. GLP-1 is expressed at the hypothalamus having regulatory functions in food intake and neuroendocrine corticoadrenal axis (HPA). Energy balance and HPA have deep influence in the gonadal function of mammals. Exendin-4 (Ex4) is a potent agonist for the GLP-1 receptor.

Objectives: To evaluate the effects of native GLP-1 (7–36)-NH2(GLP-1) and Ex4 in the function of the reproductive system in adulthood and onset of puberty in female rats.

Methods: Adult female rats were icv injected with a single dose of GLP-1/Ex4 or vehicle (Veh) in the morning of proestrous. Blood samples were taken by jugular venipuncture at different stages of the subsequent estrous cycle. Ovaries were isolated for histological studies. Another group of females was housed with males for mating that confirmed by sperm-positive vaginal plug. The dams were sacrificed by decapitation after delivery, and number of undelivered but implanted fetuses and neonates born were counted and weighed. Prepubertal rats were treatment with GLP-1/Ex4/Veh and monitoring of body weight, intake, vaginal opening (VO) and hormone levels was done.

Results: GLP-1 administration in the morning of proestrus doubled the amplitude of preovulatory LH surge and modified the estradiol and progesterone levels along the estrous cycle. That promoted a marked increase in number of Graafian follicles and corpora lutea, and consequently in litter size. Conversely, Ex4 produced a partial blockade of preovulatory LH surge, yet not affecting the number of mature follicles or corpora lutea. Administration of low doses of GLP-1 to pre-pubertal rats synchronized vaginal opening and increased LH levels. By contrast, chronic exposure to Exendin-4 produced a significant reduction in LH and complete blockade of puberty onset.

Conclusions: GLP-1 increases the preovulatory surge of gonadotropins and ovulation rate in adulthood and synchronise the onset of puberty. These effects were not reproduced by Ex4.

Disclosure: This work was supported by a grant from the Ministerio de Ciencia e Innovación, Spain (BFU 2011-27790).