Objectives: 

GLP-1, intestinal peptide, has anorexigenic and insulinotropic effects. Exendin-4 (Ex4) is a GLP-1R agonist with longer half-life than GLP-1 used in the treatment of DM2. Previous studies from our group revealed the presence of GLP-1R in the three main levels of the gonadotropic axis (hypothalamus-pituitary-gonads). In addition, GLP-1 but not Ex4 increases the magnitude of the preovulatory surge. In this study we evaluate the reproductive efficiency following administration of GLP-1 or its analogue Ex4 by quantifying the number and size of ovarian follicles in female rats, and gonadotropins and gonadal steroids levels during the estrous cycle.

Materials: 

Adult female rats were i.c.v injected with a single dose of GLP-1 (1nmol) or Ex4 (1nmol) on proestrus morning. After treatment blood samples were taken by jugular venipuncture at different stages of the estrous cycle for hormonal determinations. Ovaries were isolated for histological studies. An additional group was treated with Pregnant Mare Serum Gonadotropin (12 am at diestrus-1) and hCG (12 am at proestrus) to serve as superovulation control group.

Results: 

GLP-1 induced a significant increase in serum LH levels at 18 pm of proestrus vs. vehicle group. Conversely, Ex4 significantly decreased LH levels with the subsequent partial blockade of the preovulatory surge. However, neither GLP-1 nor Ex4 induced significative modifications on gonadal steroids circulating levels. Histology revealed that a single injection of GLP-1 duplicated the number of mature follicles vs. control but this effect was of lesser magnitude as that observed in ovaries from superovulated rats. On the contrary, Ex4 did not produced effect on folliculogenesis.

Conclusions: 

According to our results GLP-1 but not Ex4 may have a relevant role on LH secretion and folliculogenesis in the rat, improving reproductive efficiency.