GLP-1 Increases Preovulatory LH Source and the Number of Mature Follicles, As Well As Synchronizing the Onset of Puberty in Female Rats

Aug 8, 2015Endocrinology

GLP-1 Raises Preovulatory LH Levels, Increases Mature Follicles, and Helps Start Puberty at the Same Time in Female Rats

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Abstract

Acute treatment with glucagon-like peptide-1 (GLP-1) doubled the amplitude of the preovulatory LH surge in adult female rats.

GLP-1 receptor expression varies at the hypothalamus, pituitary, and ovary during the estrous cycle in adult rats.
Treatment with GLP-1 influenced estradiol and progesterone levels throughout the estrous cycle.
Acute GLP-1 treatment increased the number of Graafian follicles and corpora lutea, as well as litter size.
Exendin-4 (Ex4) reduced LH levels and partially blocked the preovulatory surge without affecting mature follicles or corpora lutea.
Chronic low-dose GLP-1 administration in prepubertal rats synchronized vaginal opening and increased LH levels without altering body weight or food intake.
Chronic exposure to Ex4 resulted in reduced ovarian and uterine weight and no vaginal opening in treated animals.

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Control of estrous cycle and reproductive capacity involves a large number of central and peripheral factors, integrating numerous nutritional and metabolic signals. Here we show that glucagon-like peptide-1 (GLP-1), a peptide with anorexigenic and insulinotropic actions, and the GLP-1 receptor agonist Exendin-4 (Ex4) exert a regulatory influence on the gonadal axis, in both adult and prepubertal female rats. In adult rats, Glp-1 receptor expression varies during the estrous cycle at the hypothalamus, pituitary, and ovary. Furthermore, acute treatment with GLP-1 in the morning proestrus doubled the amplitude of the preovulatory LH surge, as well as influencing estradiol and progesterone levels along the estrous cycle. These changes provoked an important increase in the number of Graafian follicles and corpora lutea, as well as in the litter size. Conversely, Ex4 diminished the levels of LH, later producing a partial blockade at the preovulatory surge, yet not affecting either the number of mature follicles or corpora lutea. Chronic administration of low doses of GLP-1 to prepubertal rats synchronized vaginal opening and increased LH levels on the 35th day of life, yet at these doses it did not modify their body weight, food intake, or ovarian and uterine weight. By contrast, chronic exposure to Ex4 produced a significant reduction in ovarian and uterine weight, and serum LH, and the animals treated chronically with Ex4 showed no vaginal opening in the period studied. Overall, our results demonstrate that GLP-1 and Ex4 act on the gonadal axis, involving the hypothalamic kisspeptin system, to influence reproductive efficiency in female rats.

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GLP-1 Increases Preovulatory LH Source and the Number of Mature Follicles, As Well As Synchronizing the Onset of Puberty in Female Rats

Abstract

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