Castration rapidly decreases hypothalamic γ-aminobutyric acidergic neuronal activity in both male and female rats

Yoo, Mi-Jeong; Searles, Robin V.; He, Ju‐Ren; Shen, Wei-Bin; Grattan, David R.; Selmanoff, Michael

doi:10.1016/s0006-8993(00)02600-7

Cited by 23 publications

(8 citation statements)

References 55 publications

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“…Moreover, Akema and Kimura [13] have proposed that GABA B Rs are involved in the estrogen feedback response in castrated female rats [13], while Wagner et al [48] suggested that attenuation of presynaptic GABA B autoreceptor function occurs as a consequence of an estrogen negative-feedback action. In addition, sex differences in gonadotropin increases after gonadectomy in rats [60, 61] have been attributed to GABA [62] acting at both GABA A and GABA B receptors [27]. As a consequence, we first evaluated the gonadotropin response to estrogen withdrawal (castration plus empty Silastic capsules) and reinstatement of the estradiol negative feedback (castration plus estradiol-filled Silastic capsules) in wild-type and knockout females.…”

Section: Discussionmentioning

confidence: 99%

GABAB1 Knockout Mice Reveal Alterations in Prolactin Levels, Gonadotropic Axis, and Reproductive Function

et al. 2005

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γ-Aminobutyric acid (GABA) has been implicated in the control of hypophyseal functions. We evaluated whether the constitutive loss of functional GABA_B receptors in GABA_B1 knockout (GABA_B1^–/–) 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 con trast, the estrous cyclicity was significantly disrupted in GABA_B1^–/– female mice, showing significantly extended periods in estrus and shortened periods in proestrus. Reproduction was significantly compromised in GABA_B1^–/– 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 GABA_B1^–/– females had successful pregnancies as compared with 75% in the controls. In addition, the postovariectomy LH rise was significantly advanced in GABA_B1^–/– mice, while the response to estradiol feedback was similar in both genotypes. In conclusion, our endocrine analysis of GABA_B1^–/– mice reveals that GABA_B 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.

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Section: Discussionmentioning

confidence: 99%

GABAB1 Knockout Mice Reveal Alterations in Prolactin Levels, Gonadotropic Axis, and Reproductive Function

et al. 2005

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“…In this context, it is interesting to note that LH secretion rises rapidly within 12 h following gonadectomy in the male whereas LH levels in the female take many days to reach the same concentrations [7, 8, 9, 29]. Thus, it would appear that a more rapidly reversible gonadal steroid negative feedback mechanism exists in the male compared with the female.…”

Section: Discussionmentioning

confidence: 99%

“…Investigations have further demonstrated that GABA acts principally through GABA A receptors located within the vicinity of the GnRH cell bodies to modulate LH secretion [17, 18, 19, 20, 24]and both electron-microscopic [25]and GABA A receptor subunit colocalization [26, 27]studies indicate the presence of GABA A receptors on GnRH neurons in the female rat. Although it is not known if sex differences exist in the direct GABAergic regulation of the GnRH neurons, sex differences in GABA turnover have been reported in the rat preoptic area [28, 29]and whole brain GABA manipulation exerts sexually dimorphic effects of on LH secretion [30]. …”

Section: Introductionmentioning

confidence: 99%

Profiling γ-Aminobutyric Acid (GABAA) Receptor Subunit mRNA Expression in Postnatal Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mouse with Single Cell RT-PCR

Pape¹,

Skynner²,

Sim³

et al. 2001

Neuroendocrinology

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The present investigation has examined which subunits of the GABA_A receptor are expressed by gonadotropin-releasing hormone (GnRH) neurons in the juvenile and adult male mouse. Cells of defined morphology, located in the medial septum (MS) and rostral preoptic area (POA), were patch-clamped in the acute brain slice preparation and their cell contents extracted. A reverse transcriptase polymerase chain reaction (RT-PCR) procedure using nested primers was used to establish individual GnRH mRNA-expressing cells which were then evaluated for eleven GABA_A receptor (α1–5, β1–3, γ1–3) subunit transcripts. Single and multiple GABA_A receptor subunit mRNAs were detected in approximately 70% of all GnRH neurons. A range of different subunit mRNAs (α1, α2, α5, β1, β2, β3, γ2) were found in juvenile GnRH neurons, with the α1γ2 and α5γ2 combinations encountered most frequently within individual cells. The expression profile in adult GnRH neurons was more extensive than that detected in juveniles with α1, α2, α3, α5, β1, β2, β3, γ1 and γ2 subunits all being detected. The major difference in subunit profile between GnRH neurons located in the MS and POA involved the β subunits. The principal postnatal developmental change was one of increasing overall subunit heterogeneity in maturing POA GnRH neurons. The profile of GABA_A receptor subunit mRNAs detected in male GnRH neurons was quite different to that reported by us for female GnRH neurons in the mouse using the same RT-PCR approach. Together, these findings indicate that postnatal GnRH neurons are likely to express a range of GABA_A receptor subunit mRNAs in a sexually dimorphic and developmentally-regulated manner.

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“…It is possible that the sustained inhibition of LH secretion by progesterone could also involve stimulation of GABAergic neurons in the rostral hypothalamus. It has been demonstrated that GABA activity in these regions is rapidly suppressed following ovariectomy in cycling female rats [30], suggesting a role for GABA in mediating negative-feedback actions of ovarian steroids. Alternatively, subpopulations of GABAergic neurons in the preoptic region may respond to the suckling stimulus at different rates, accounting for the continued suppression of LH levels, relative to nonlactating rats, even after suckling had ceased for 4 h. Hence, further changes in GABA turnover might be observed after longer periods of nonsuckling, or in the absence of ovarian hormones.…”

Section: Discussionmentioning

confidence: 99%

Lactation Alters γ-Aminobutyric Acid Neuronal Activity in the Hypothalamus and Cerebral Cortex in the Rat

Kornblatt¹,

Grattan²

2001

Neuroendocrinology

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γ-Aminobutyric acid (GABA) neurons terminating in the hypothalamus have been implicated in the neuroendocrine regulation of reproductive hormones, particularly luteinizing hormone (LH) and prolactin. The aim of this study was to examine whether GABAergic neuronal activity in the hypothalamus was modified during lactation, and whether any observed changes correlated with changes in secretion of these hormones. Animals were divided into three experimental groups: diestrous controls, lactating with pups present (with pups), and lactating with pups removed for 4 h (without pups). Animals were decapitated either without treatment, or 60 min after inhibition of GABA degradation by aminooxyacetic acid (AOAA) (100 mg/kg, i.p.). The rate of GABA accumulation in the tissue after AOAA is a measure of GABA turnover. GABA turnover was estimated in 13 microdissected brain regions, and serum prolactin and LH measured by radioimmunoassay. Suckling was associated with significantly increased prolactin and significantly decreased LH compared with diestrous rats. In lactating rats with pups, GABA turnover was significantly increased in the cingulate cortex compared with diestrous rats. GABA turnover was significantly increased in the ventrolateral preoptic nucleus of lactating rats with pups compared with diestrous rats or lactating rats without pups. There was significantly lower GABA turnover in the anterior hypothalamic area, ventromedial and dorsomedial hypothalamic nuclei in lactating rats without pups compared with diestrous rats. There were no significant changes in other brain regions examined. The results demonstrate that activity of GABAergic neurons in specific parts of the hypothalamus and cerebral cortex is altered during lactation.

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Castration rapidly decreases hypothalamic γ-aminobutyric acidergic neuronal activity in both male and female rats

Cited by 23 publications

References 55 publications

GABA<sub>B1</sub> Knockout Mice Reveal Alterations in Prolactin Levels, Gonadotropic Axis, and Reproductive Function

GABA<sub>B1</sub> Knockout Mice Reveal Alterations in Prolactin Levels, Gonadotropic Axis, and Reproductive Function

Profiling γ-Aminobutyric Acid (GABA<sub>A</sub>) Receptor Subunit mRNA Expression in Postnatal Gonadotropin-Releasing Hormone (GnRH) Neurons of the Male Mouse with Single Cell RT-PCR

Lactation Alters γ-Aminobutyric Acid Neuronal Activity in the Hypothalamus and Cerebral Cortex in the Rat

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