GABAB1 knock-out mice reveal alterations in prolactin levels, the gonadotropin axis and reproductive function

PAOLO N. CATALANO; MARÍA MARTA BONAVENTURA; PATRICIA SILVEYRA; BERNHARD BETTLER; CARLOS LIBERTUN; VICTORIA A. LUX-LANTOS

NEUROENDOCRINOLOGY

Karger

Lugar: Basel; Año: 2005 vol. 82 p. 294 - 305

0028-3835

GABA has been implicated in the control of hypophyseal function. We evaluated whether the constitutive loss of functional GABAB receptors in GABAB1 knock-out(GABAB1-/-) mice alters hormonal levels, under basal and stimulated conditions levels, and reproductive function. Serum hormone levels were measured by RIA, cyclicity was evaluated by vaginal lavages, and mating behavior was determined by the presence of vaginal plugs. A moderate hyperprolactinemic condition was observed only in male GABAB1-/- mice, while the immobilization stress-induced PRL increase and TSH decrease were similar between genotypes. Basal LH, FSH, TSH and GH levels were similar between genotypes in each sex. Analysis of the gonadotropin axis revealed no differences in puberty onset between female genotypes. In contrast, estrous cyclicity was significantly disrupted in GABAB1-/- female mice, which showed significantly extended periods in estrus and shortened periods in proestrus. Reproduction was significantly compromised in GABAB1-/- females, with a significantly lower percentage of mice (37.5%) getting pregnant in the first 30 days of male exposure as compared to wild-type controls (87.5%). Moreover, only 14% of vaginal plug-positive GABAB1-/- females showed successful pregnancies compared to 75% in controls. In addition, the post-ovariectomy LH rise was significantly advanced in GABAB1-/- mice, while the response to estradiol feed-back was similar in both genotypes. In conclusion, our endocrine analysis of GABAB1-/- mice reveals that GABAB receptors are involved in the regulation of basal prolactin titers. Moreover, the hypothalamic–hypophyseal-ovarian axis is seriously disturbed, with alterations in cyclicity, the postcastration LH increase and fertility indexes. The molecular mechanism underlying these hormonal disturbances remains to be addressed.