Biomedical subjects

D R Grattan

Publications and source records attributed to D R Grattan.

At least 37 records · Page 2Linked to original sources

PubMed2000

Decreasing GAD neonatally attenuates steroid-induced sexual differentiation of the rat brain.

During development, exposure to gonadal steroids results in brain sexual differentiation. Postnatally, hypothalamic gamma-aminobutyric acid (GABA) levels are almost double in males versus females. We hypothesized that increased GABA neonatally results in masculinization. Males, females, and androgenized females were infused intrahypothalamically with antisense oligonucleotides against glutamic acid decarboxylase (GAD) mRNA at birth to reduce GABA synthesis. GAD protein and GABA levels were reduced 24 hr later without obvious toxic effects, as determined by histological examination. As adults, neonatally antisense-treated, androgenized females showed reduced intromission-like behavior and lordosis quotients compared with vehicle and scrambled controls. Lordosis quotients were reduced about 50% in nonandrogenized females versus vehicle and scrambled controls. These data suggest that GABA is involved in mediating brain sex differentiation and may act in both males and females.

Adrenal Cortex Hormones↗

PubMed1999

STAT5b-deficient mice are growth hormone pulse-resistant. Role of STAT5b in sex-specific liver p450 expression.

The signal transducer and transcriptional activator STAT5b is required to maintain the adult male pattern of liver gene expression and whole body pubertal growth rates, as demonstrated by the loss of these growth hormone (GH) pulse-dependent responses in mice with a targeted disruption of the STAT5b gene. The present study investigates whether these phenotypes of STAT5b-deficient mice result from impaired intracellular GH signaling associated with a loss of GH pulse responsiveness, as contrasted with a feminization of the pituitary GH secretory profile leading to the observed feminization of body growth and liver gene expression. Pulsatile GH replacement in hypophysectomized mice stimulated body weight gain in wild-type but not in STAT5b-deficient mice. Expression of the male-specific liver P450 enzyme CYP2D9, which is reduced to female levels in hypophysectomized male mice, was restored to male levels by GH pulse replacement in wild-type but not in STAT5b-deficient mice. Similarly, a female-specific liver CYP2B P450 enzyme that was up-regulated to female levels following hypophysectomy of males was suppressed to normal basal male levels by GH pulses only in wild-type hypophysectomized mice. Finally, urinary excretion of the male-specific, GH pulse-induced major urinary protein was restored to normal male levels following pulsatile GH treatment only in the case of wild-type hypophysectomized mice. STAT5b-deficient mice are thus GH pulse-resistant, supporting the proposed role of STAT5b as a key intracellular mediator of the stimulatory effects of plasma GH pulses on the male pattern of liver gene expression.

Animals↗

PubMed1999

Increased prolactin receptor immunoreactivity in the hypothalamus of lactating rats.

Prolactin (PRL) exerts numerous effects in the brain including induction of maternal behaviour, increased food intake, and inhibition of GnRH secretion. Knowledge about the distribution of PRL receptors (PRL-R) in the brain will be critical for investigating mechanisms of PRL-brain interactions during lactation. The present study aimed to investigate the distribution of PRL-R in specific hypothalamic nuclei of lactating rats by immunohistochemistry and to compare this distribution with that in dioestrous rats. Rats were perfused with 2% paraformaldehyde and brains were cut into coronal sections (18 microm) for immunostaining. Immunoreactivity was detected by the avidin biotin complex method using mouse monoclonal antibody U5. In dioestrous rats, PRL-R immunoreactivity was observed in the choroid plexus, three hypothalamic nuclei: medial preoptic, periventricular and arcuate, and in the median eminence. The number of labelled profiles per section in the medial preoptic and arcuate nuclei increased significantly (P<0.05) in lactating rats (days 7-10 to post partum) when compared with dioestrous rats. Furthermore, in lactating rats, PRL-R immunoreactive neurons were identified in the cerebral cortex, substantia nigra and numerous additional hypothalamic nuclei including the ventromedial preoptic, ventrolateral preoptic, lateroanterior hypothalamic, ventrolateral hypothalamic, paraventricular hypothalamic, supraoptic, suprachiasmatic, and ventromedial hypothalamic nuclei. These observations assist our understanding of the multiple sites of PRL effects on brain function during lactation.

Animals↗

PubMed1999

Expression of prolactin receptor mRNA is increased in the preoptic area of lactating rats.

This study investigated expression of prolactin receptor (PRL-R) mRNA in the preoptic area in midlactating rats compared with diestrous rats. Tissues from specific nuclei were micropunched from 300-microm thick rat brain sections with 300- or 500-microm diameter needles. After total RNA was extracted, the two forms of PRL-R mRNA were evaluated by reverse transcriptase polymerase chain reaction and Southern hybridization. The results showed that levels of long-form PRL-R mRNA in the ventrolateral preoptic nucleus and lateroanterior nucleus in lactating rats were significantly higher (p < 0.05) than in diestrous rats. The ventromedial and medial preoptic nuclei in lactating rats also expressed moderately high levels of long-form mRNA when compared with (p = 0.0547) diestrous rats. The ventromedial and ventrolateral preoptic nuclei, and ventrolateral hypothalamic nucleus in lactating rats expressed significantly higher levels of short-form mRNA than in diestrous rats. The increased expression of both forms of PRL-R mRNA helps explain numerous effects of PRL on brain functions during lactation.

Animals↗

PubMed1999

Increased expression of both short and long forms of prolactin receptor mRNA in hypothalamic nuclei of lactating rats.

This study investigated expression of prolactin receptor (PRL-R) mRNA in selected hypothalamic nuclei of lactating rats (days 7-10 post partum) compared with dioestrous rats. Rat brains were frozen with liquid nitrogen and cut into coronal sections of 300 microm. From these sections, tissues were micropunched from the parietal cortex (CTX), choroid plexus (ChP), and five hypothalamic regions: supraoptic (SO), paraventricular (Pa), arcuate (Arc) and ventromedial hypothalamic (VMH) nuclei, and median eminence (ME). Expression of both short and long forms of PRL-R mRNA were evaluated by reverse transcription-PCR and Southern hybridisation. The results showed that the relative amount of short form mRNA in the ChP of lactating rats was significantly higher than in dioestrous rats. The short form of PRL-R mRNA was undetectable in the SO, Pa, VMH of dioestrous rats but was expressed at a significant level in lactating rats. Levels of long form mRNA in the ChP, SO, Pa and VMH in lactating rats were significantly increased compared with dioestrous rats. Moreover, the long form mRNA was induced in the CTX of lactating rats. In the Arc, levels of both forms of PRL-R mRNA tended to increase in lactating rats compared with dioestrous rats but changes were not statistically significant. Neither form of PRL-R mRNA was detectable in the ME in the two animal models. Increased expression of PRL-R mRNA in specific brain regions during lactation is consistent with the variety of PRL effects on the brain, and may help to explain profound physiological changes in the lactating mother.

Animals↗

PubMed1998

Differential expression of the two forms of prolactin receptor mRNA within microdissected hypothalamic nuclei of the rat.

The prolactin receptor (PRL-R) has recently been identified in various hypothalamic nuclei of female rats. In this study, expression of both the short- and long-forms of PRL-R mRNA was investigated in 11 microdissected hypothalamic nuclei of ovariectomized, estrogen-treated rats. Specific nuclei were micropunched from 300-micrometer thick frozen coronal sections with autoclaved stainless steel needles of 300 or 500 micrometer diameter. Total RNA was extracted from the punched tissue, and the two forms of PRL-R mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) using specific primers. The RT-PCR product was verified by Southern hybridization with a digoxigenin-labelled oligonucleotide probe common to both forms. The results showed that both forms of PRL-R mRNA were expressed to varying degrees in the choroid plexus, cerebral cortex and various hypothalamic nuclei, including: ventromedial preoptic nucleus, ventrolateral preoptic nucleus, medial preoptic nucleus, suprachiasmatic nucleus, supraoptic nucleus, paraventricular hypothalamic nucleus, periventricular hypothalamic nucleus, arcuate nucleus, ventromedial hypothalamic nucleus, and median eminence. Of these brain regions, the choroid plexus expressed the highest level while the suprachiasmatic nucleus contained the lowest level of mRNA. There was no expression detected in the dorsomedial hypothalamic nucleus. The choroid plexus, supraoptic nucleus and paraventricular hypothalamic nucleus had higher levels of the short-form of the PRL-R mRNA than the long-form, whilst other hypothalamic nuclei preferentially expressed the long-form of the PRL-R mRNA. The differential expression of PRL-R gene suggests that the two forms may be differentially regulated in specific brain regions and may mediate different functions of PRL.

Animals↗

PubMed1998

Distribution of prolactin receptor immunoreactivity in the brain of estrogen-treated, ovariectomized rats.

Although there is extensive evidence for effects of prolactin (PRL) on the brain, knowledge about the PRL receptor (PRL-R) in the brain is limited. By using monoclonal antibodies raised against purified rat liver PRL-R, the distribution of PRL-R was investigated by immunohistochemistry in brains of the estrogen-treated ovariectomized (OVX+E) rat and the adult male rat. Immunohistochemistry was performed by using the avidin biotinylated horse radish peroxidase macromolecular complex method. In both male and OVX+E rats, strong immunostaining was detected in the choroid plexus of all cerebral ventricles. This immunostaining was localized predominately on epithelial cell membranes. In the OVX+E female rat, scattered immunoreactive perikarya were observed in the arcuate nucleus, periventricular hypothalamic nucleus, preoptic area, suprachiasmatic nucleus, and supraoptic nucleus of the hypothalamus. Immunostaining in hypothalamic nuclei was localized on neuronal cell bodies as well as on neuronal processes. In addition, there was extensive PRL-R immunoreactivity throughout the globus pallidus and ventral pallidum. Immunostaining in these striatal regions was not associated with neuronal cell bodies but appeared to be localized on processes or glial cells. In the male rat, less immunostaining was observed in the hypothalamus, and there was no immunostaining in the corpus striatum. No significant staining was observed in the cerebral cortex, thalamus, or hindbrain of either male or OVX+E rats. The implication of PRL-R existence in these brain regions remains to be investigated.

Animals↗

PubMed1997

Sex differences in the activity of gamma-aminobutyric acidergic neurons in the rat hypothalamus.

The rate of GABA turnover was determined in nine microdissected brain regions in adult male and female rats. In the medial preoptic nucleus (central aspect) and ventromedial nucleus (ventrolateral aspect) of the hypothalamus, areas involved in the regulation of gonadotropin secretion and sex behavior, GABAergic neuronal activity was about 2-fold greater in males than females. These results demonstrate a striking sexual dimorphism in the activity of specific populations of hypothalamic GABAergic neurons.

Animals↗

PubMed1997

Gonadal hormones alter hypothalamic GABA and glutamate levels.

GABA and glutamate levels were measured in brain sites important for lordotic responding and in other hypothalamic sites after gonadal hormone treatments sufficient to activate lordosis. Estradiol increased GABA and glutamate in the ventromedial nucleus and the vertical diagonal bands. Progesterone administration to estradiol primed females led to a rapid decline of the transmitters in these areas. Results are discussed in relation to neuroendocrine regulation.

Animals↗

PubMed1996

GABAergic neuronal activity and mRNA levels for both forms of glutamic acid decarboxylase (GAD65 and GAD67) are reduced in the diagonal band of Broca during the afternoon of proestrus.

There is considerable evidence that GABAergic neurons play an important role in the regulation of gonadotropin-releasing hormone (GnRH) secretion, and that these neurons may mediate the feedback actions of gonadal steroids on GnRH neurons. The aim of the present study was to investigate whether endogenous changes in ovarian steroid secretion during the estrous cycle influenced GABAergic neuronal activity in the preoptic region of the hypothalamus, and in other steroid-sensitive brain regions. Intact, adult female rats were sacrificed at various times during the days of metestrus or proestrus. GABAergic neuronal activity was estimated by measuring the rate of accumulation of GABA in microdissected brain regions after pharmacological inhibition of GABA degradation. Concentrations of mRNA for both forms of glutamic acid decarboxylase (GAD65 and GAD67) were quantified in microdissected brain regions by a microlysate ribonuclease protection assay. In the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis (DBB(ovlt)), GABAergic neuronal activity was significantly reduced during the afternoon of proestrus compared with the morning of either proestrus or metestrus. In the lateral septal nucleus, GABAergic neuronal activity was significantly increased in the afternoon of proestrus compared with the morning. There were no significant effects of time of day or day of estrous cycle in the medial preoptic nucleus, median eminence, ventromedial nucleus, suprachiasmatic nucleus, medial septal nucleus, hippocampus (CA1 region), or cingulate cortex. In the DBB(ovlt), mRNA levels for both GAD65 and GAD67 were significantly reduced in the afternoon of proestrus compared with the afternoon of metestrus. By contrast, there was no change in GAD65 and GAD67 mRNA levels in the cingulate cortex at any of the times examined. These results demonstrate that GABAergic neuronal activity, and mRNA levels for both GAD65 and GAD67, are reduced in the DBB(ovlt) during the afternoon of proestrus. These results support the hypothesis that decreased GABAergic neuronal activity in this region plays a major permissive role in the generation and maintenance of the estrogen-induced LH surge.

Animals↗

PubMed1996

Sex differences in glutamic acid decarboxylase mRNA in neonatal rat brain: implications for sexual differentiation.

Sexual differentiation of rodent brain is dependent upon hormonal exposure during a "critical period" beginning in late gestation and ending in early neonatal life. Steroid hormone action at this time results in anatomical and physiological sexual dimorphisms in adult brain, but the mechanism mediating these changes is essentially unknown. The inhibitory neurotransmitter, GABA, is involved in regulation of sexually dimorphic patterns of behavior and gonadotropin secretion in the adult. Recent evidence suggests that during development GABA is excitatory and provides critical neurotrophic and neuromodulatory influences. We hypothesized that steroid-induced changes in GABAergic neurotransmission during this critical period are important mediators of sexual differentiation in brain. Therefore, we quantified levels of mRNA for GAD, the rate-limiting enzyme in GABA synthesis. On Postnatal Day 1, males had significantly higher levels of GAD mRNA in the dorsomedial nucleus, arcuate nucleus, and CA1 region of hippocampus. On Postnatal Day 15, after the critical period for sexual differentiation has ended, these differences were no longer present. We examined the role of gonadal steroids in regulating GAD by removing testes of males and administering testosterone to females at birth. Exposure to testosterone was correlated with increased GAD mRNA in the dorsomedial nucleus. A sex difference in GAD mRNA was also observed in the medial preoptic area, but the influence of testosterone was inconclusive. We conclude that sex differences in the GABAergic system during development are partially hormonally mediated, and that these differences may contribute to the development of sexually dimorphic characteristics in adult brain.

Animals↗

PubMed1996

Hormonal and neurotransmitter regulation of GnRH gene expression and related reproductive behaviors.

Gonadotropin-releasing hormone (GnRH), having a highly conserved structure across mammalian species, plays a pivotal role in the control of the neuroendocrine events and the inherent sexual behaviors essential for reproductive function. Recent advances in molecular genetic technology have contributed greatly to the investigation of several aspects of GnRH physiology, particularly steroid hormone and neurotransmitter regulation of GnRH gene expression. Behavioral studies have focused on the actions of GnRH in steroid-sensitive brain regions to understand better its role in the facilitation of mating behavior. To date, however, there are no published reports which directly correlate GnRH gene expression and reproductive behavior. The intent of this article is to review the current understanding of the way in which changes in GnRH gene expression, and modifications of GnRH neuronal activity, may ultimately influence reproductive behavior.

Animals↗

PubMed1996

Antiandrogen microimplants into the rostral medial preoptic area decrease gamma-aminobutyric acidergic neuronal activity and increase luteinizing hormone secretion in the intact male rat.

gamma-Aminobutyric acid (GABA)ergic neurons terminating in the rostral hypothalamus are stimulated by testosterone. To investigate whether this action is mediated locally through androgen receptors in the rostral hypothalamus, bilateral microcannulas (28 gauge) containing the androgen receptor antagonist, hydroxyflutamide (HF), were stereotaxically implanted into the rostral medial preoptic area (rMPA) just dorsal to the major population of GnRH cell bodies. Two days later, blood samples were collected for assay of LH, and animals were killed for determination of GABAergic neuronal activity in tissue dissected from the site of the implanted cannulas. Animals were decapitated either without treatment or 60 min after inhibition of GABA degradation by aminooxyacetic acid (100 mg/kg, ip). The rate of GABA accumulation in the tissue after aminooxyacetic acid treatment was used as a measure of GABA turnover. Levels of messenger RNA for both forms of glutamic acid decarboxylase (GAD65 and GAD67), the rate-limiting enzyme responsible for GABA synthesis also were measured by a microlysate ribonuclease protection assay. LH levels were significantly increased (1.8-fold) in HF-treated animals compared with controls. In the MPA, beneath the implant cannulas, GABA turnover was significantly reduced in HF-treated rats. There was no effect of treatment in the frontal cortex, which was used as a control region. Surprisingly, levels of messenger RNA for both GAD65 and GAD67 were significantly increased in HF-treated rats. The results indicate that GABAergic neurons terminating in the rostral hypothalamus are tonically stimulated by testosterone acting by means of androgen receptors localized in this region. These findings support the working hypothesis that androgen-sensitive GABAergic neurons in the rMPA mediate the negative feedback action of testosterone on GnRH secretion in the male rat.

Androgen Antagonists↗

PubMed1995

Absence of short-loop autoregulation of prolactin during late pregnancy in the rat.

Animals bearing intrahypothalamic anterior pituitary (AP) grafts exhibit a central hyperprolactinemia, and thus, serve as a model for the study of short-loop feedback regulation of prolactin (PRL) secretion. We investigated the effects of intrahypothalamic AP grafts on PRL secretion during late pregnancy (n = 7). A further group of five rats was injected with the dopamine against bromocriptine during late pregnancy and five control rats were treated with the bromocriptine-vehicle only. A nocturnal surge in plasma PRL concentrations was observed in the vehicle-injected control animals, peaking at 212 +/- 11 ng/ml at 0300 h on the day of parturition. Despite the central hyperprolactinemia due to the grafts, a similar PRL surge was observed in grafted animals, peaking at 205 +/- 35 ng/ml at 0300 h on the day of parturition. Bromocriptine treatment completely blocked the nocturnal surge of PRL. These results suggest that short-loop feedback autoregulation of PRL secretion becomes less responsive or nonfunctional in the last 24 h of pregnancy in the rat. This apparent change in sensitivity of the autofeedback mechanism may be an important physiological mechanism to allow the hypersecretion of PRL during lactation.

Animals↗

PubMed1995

Orchidectomy and NMDA increase GnRH secretion as measured by push-pull perfusion of rat anterior pituitary.

Using push-pull perfusion to measure concentrations of gonadotropin-releasing hormone (GnRH) in the extracellular fluid of the anterior pituitary gland of the male rat, we have measured GnRH release at specific times before and after castration and in response to acute administration of N-methyl-D-aspartate (NMDA). After castration (7 days), mean GnRH levels were substantially increased (4.3-fold) compared with intact controls (0.94 +/- 0.16 vs. 0.22 +/- 0.08 pg/10 min, respectively, P < 0.05) due to an increase in both the frequency and amplitude of GnRH pulses. Testosterone partially reduced GnRH release (0.62 +/- 0.10 pg/10 min). NMDA induced a rapid increase in plasma luteinizing hormone (LH) in both intact and castrated rats and increased GnRH concentrations in the perfusion samples (P < 0.05). There was no change in LH release induced by two doses of injected GnRH (5 and 25 ng/100 g body wt) 2 days after castration, but by 6 days after castration the response to both doses was significantly increased. These results demonstrate that GnRH release in the male rat is acutely increased by NMDA and is chronically increased after orchidectomy. Increased pituitary sensitivity to GnRH also contributes to the hypersecretion of LH after castration, particularly at longer times after removal of testosterone negative feedback.

Animals↗

PubMed1994

Castration-induced decrease in the activity of medial preoptic and tuberoinfundibular GABAergic neurons is prevented by testosterone.

We recently determined that castration specifically decreased GABA turnover in discrete rostral and mediobasal hypothalamic structures. This study aimed to investigate whether testosterone could stimulate GABAergic neuronal activity in these hypothalamic GABAergic neurons in the castrate rat, and to compare the effects of episodic testosterone replacement with the constant levels provided by subcutaneous testosterone implants. Animals were divided into 4 experimental groups: intact, 48 h castrate, 48 h castrate+testosterone capsules (2 x 30 mm Silastic implants, 1.57 mm ID, 3.18 mm OD) and 48 h castrate+testosterone injections (100 micrograms/injection s.c., every 8 h). GABA concentrations were measured in 4 microdissected brain regions either before or 60 min after inhibition of the GABA degrading enzyme, GABA transaminase, by injection of aminooxyacetic acid (AOAA, 100 mg/kg i.p.). The rate of GABA accumulation in the tissue following injection of AOAA was used as an index of GABAergic neuronal activity. Castration resulted in a 10-fold increase in serum LH concentrations compared with intact rats. Either mode of testosterone administration completely prevented this castration-induced LH rise. In the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis, the medial preoptic nucleus and in the median eminence, GABA turnover was significantly reduced by castration to approximately 50% that of intact rats. Either testosterone implants or testosterone injections prevented this castration-induced decrease in GABA turnover, such that the turnover rates were not significantly different from intact rats. There was no effect of castration with or without testosterone replacement in the cingulate cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Prolactin- and testosterone-induced inhibition of LH secretion after orchidectomy: role of preoptic and tuberoinfundibular gamma-aminobutyric acidergic neurones.

The inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) may play an important role in the regulation of LH-releasing hormone secretion. The present study examined the effect of prolactin on GABAergic neuronal activity in microdissected brain regions of the orchidectomized rat, to determine whether inhibition of LH secretion after castration by acute hyperprolactinaemia was associated with prolactin-induced changes in GABAergic neuronal activity. The effects of prolactin were contrasted with the effects of testosterone on hypothalamic GABAergic neurones after orchidectomy. GABA concentrations were measured by high pressure liquid chromatography in eight microdissected brain regions in untreated rats and 60 min after inhibition of the GABA catabolic enzyme GABA transaminase by injection of amino-oxyacetic acid (AOAA). The rate of GABA accumulation in microdissected brain regions following injection of AOAA was taken as an index of GABAergic neuronal activity. Rats were divided into seven experimental groups: intact controls, 2 days after castration, 2 days after castration with prolactin treatment (2.5 mg ovine prolactin injected s.c. every 12 h, starting at the time of castration), 2 days after castration with testosterone replacement (30 mm silicone elastomer implant containing crystalline testosterone), 6 days after castration, 6 days after castration with prolactin treatment, and 6 days after castration with testosterone replacement. Both 2 and 6 days after castration, plasma LH was markedly elevated above levels in intact rats, and AOAA-induced GABA accumulation was significantly decreased in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis, in the medial preoptic nucleus and in the median eminence. Hyperprolactinaemia significantly reduced LH levels 2 days but not 6 days after castration. GABAergic neuronal activity, however, was not significantly affected by prolactin at either time. Testosterone replacement blocked the postcastration elevation in plasma LH and prevented the castration-induced suppression of GABAergic neuronal activity both 2 and 6 days after castration. There were no castration- or hormone-induced changes in GABAergic neurones observed in the medial or lateral septum, caudate nucleus, cingulate cortex or arcuate nucleus. These results demonstrate that the activity of GABAergic neurones terminating in the rostral hypothalamus and the median eminence is positively regulated by testosterone, and that these steroid-sensitive GABAergic neurones may be important in the negative-feedback control of LH secretion. Inhibition of LH secretion by hyperprolactinaemia, however, may not be mediated by changes in GABAergic neuronal activity.

Animals↗

PubMed1993

Regional variation in gamma-aminobutyric acid turnover: effect of castration on gamma-aminobutyric acid turnover in microdissected brain regions of the male rat.

This study compared the turnover of GABA neurons in different brain areas of the male rat and examined the effect of castration on GABA turnover in regions of the brain associated with the control of gonadotropin secretion. To estimate GABA turnover, GABA was quantified by HPLC in microdissected brain regions 0, 30, 60, 90, and 120 min after inhibition of GABA degradation by aminooxyacetic acid (100 mg/kg, i.p.). GABA accumulation was linear in all areas for 90 min (p < 0.01), and GABA turnover was estimated as the slope of the line formed by increased GABA concentration versus time, determined by linear regression. There was considerable regional variation both in the initial steady-state concentrations of GABA and in the rates of GABA turnover. Of 10 discrete brain structures, GABA turnover was highest in the medial preoptic nucleus and lowest in the caudate nucleus. Turnover times in the terminal fields of known GABAergic projection neurons ranged sevenfold, from 2.6 h in the substantia nigra to 0.4 h in the lateral vestibular nucleus. The effect of castration on GABA turnover in 13 microdissected brain regions was investigated by measuring regional GABA concentrations before and 30 min after injection of aminooxyacetic acid in intact rats or 2 or 6 days postcastration. Following castration, steady-state GABA concentrations were increased, and GABA turnover decreased in the diagonal band of Broca, the medial preoptic area, and the median eminence. GABA turnover increased in the medial septal nucleus and was unaffected in the cortex, striatum, and hindbrain. These results are consistent with the hypothesis that testosterone negative-feedback control of luteinizing hormone-releasing hormone involves steroid-sensitive GABAergic neurons in the rostral and medial basal hypothalamus.

Aminooxyacetic Acid↗