GABAB1 knockout mice reveal alterations in prolactin levels, gonadotropic axis, and reproductive function

Paolo N. Catalano, María Marta Bonaventura, Patricia Silveyra, Bernhard Bettler, Carlos Libertun, Victoria A. Lux-Lantos

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

γ-Aminobutyric acid (GABA) has been implicated in the control of hypophyseal functions. We evaluated whether the constitutive loss of functional GABAB receptors in GABAB1 knockout (GABAB1 -/-) mice alters hormonal levels, under basal and stimulated conditions, and reproductive function. The serum hormone levels were measured by radioimmunoassay, the estrous cyclicity was evaluated by vaginal lavages, and the mating behavior was determined by the presence of vaginal plugs. A moderate hyperprolactinemic condition was observed, in which prolactin increase and thyroid-stimulating hormone decrease were similar between genotypes. Basal luteinizing hormone (LH), follicle-stimulating hormone, thyroid-stimulating hormone, and growth hormone levels were similar between genotypes in each sex. Analysis of the gonadotropin axis revealed no differences in puberty onset between female genotypes. In contrast, the estrous cyclicity was significantly disrupted in GABAB1-/- female mice, showing significantly extended periods in estrus and shortened periods in proestrus. Reproduction was significantly compromised in GABAB1-/- females, with a significantly lower proportion of mice (37.5%) getting pregnant during the first 30 days of mating as compared with wild-type controls (87.5%). Moreover, only 14% of vaginal plug positive GABAB1-/- females had successful pregnancies as compared with 75% in the controls. In addition, the postovariectomy LH rise was significantly advanced in GABAB1 -/- mice, while the response to estradiol feedback 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, postcastration LH increase, and fertility indexes. The molecular mechanism underlying these hormonal disturbances remains to be addressed.

Original languageEnglish (US)
Pages (from-to)294-305
Number of pages12
JournalNeuroendocrinology
Volume82
Issue number5-6
DOIs
StatePublished - May 2006

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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