GABA control of LHRH release is dependent on the steroid milieu

McRee, R; Meyer, Donald C.

doi:10.1016/0304-3940(93)90743-5

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…Among these, GABA plays a major role as an inhibitory amino acid. It has been demonstrated that perifusion of hypothalamic fragments in vitro with GABA resulted in diminished GnRH secretion (36). Furthermore, i.c.v.…”

Section: Discussionmentioning

confidence: 99%

Changes of Expression of Genes Related to the Activity of the Gonadotrophin‐Releasing Hormone Pulse Generator in Young Versus Middle‐Aged Male Rats

Böttner

Leonhardt

Wuttke

et al. 2007

J Neuroendocrinology

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In females, it is well established that changes in the expression of neurotransmitters and peptides regulating the activity of the gonadotrophin-releasing hormone (GnRH) pulse generator are altered during ageing. By contrast, little is known about whether those age-related changes also occur in males. Therefore, we designed an animal study with orchidectomised young and middle-aged male rats to investigate changes in luteinising hormone (LH) secretion profiles and changes in the mRNA expression of genes regulating the activity of the GnRH pulse generator. Our results demonstrate that middle-aged rats exhibit lower serum LH levels and relatively fewer LH pulses with attenuated amplitude compared to young animals. Furthermore, upon ageing, GnRH mRNA expression is up-regulated in the preoptic area and the septum where GnRH neurones reside. Analysis of mRNA levels of glutamate decarboxylase (GAD) enzymes revealed that GAD(65) and GAD(67) mRNA expression increased in the mediobasal hypothalamus (MBH) and that GAD(67) mRNA levels decreased in the suprachiasmatic nucleus. In addition, we observed an age-related increase of oestrogen receptor (ER)alpha mRNA in the MBH, and both ERalpha and ERbeta mRNA expression was up-regulated in the pituitary of middle-aged rats compared to young animals. Taken together, our data support the existence of a male 'andropause' that is, like the menopause in females, accompanied by changes in neurotransmitter and hormone receptor expression that are involved in regulating the function of the GnRH pulse generator.

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Section: Discussionmentioning

confidence: 99%

Changes of Expression of Genes Related to the Activity of the Gonadotrophin‐Releasing Hormone Pulse Generator in Young Versus Middle‐Aged Male Rats

Böttner

Leonhardt

Wuttke

et al. 2007

J Neuroendocrinology

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“…In adult animals, gonadal steroids inhibit LH secretion by decreasing the activity of neurons in the mediobasal hypothalamus (O'Bryne et al 1993), resulting in a decrease in LHRH biosynthesis (Toranzo et al 1989) and release (Karsch et al 1987). Since LHRH neurons do not contain estrogen receptors, these inhibitory effects of estradiol on LHRH biosynthesis and release are complex and probably involve an interneuronal pathway (Herbison et al 1995, Sullivan et al 1995, possibly the activation of the inhibitory neurotransmitter -aminobutyric acid (GABA) in discrete hypothalamic neurons (Herbison et al 1991, McRee & Meyer 1993. The expression of estrogen receptors on GABAergic and glutamate neurons increases developmentally in female monkeys (Thind & Goldsmith 1997).…”

Section: Discussionmentioning

confidence: 99%

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys

Wilson

1998

Journal of Endocrinology

109

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Previous data suggest that developmental increases in peripheral concentrations of insulin-like growth factor-I (IGF-I) may be one of several neuroendocrine signals that regulate the timing of puberty. In order to test this hypothesis further, normal juvenile female rhesus monkeys (Con; n=6) were compared with age-matched animals (Igf; n=4) which received a constant subcutaneous infusion of recombinant human IGF-I (110 µg/kg/day) from 18 through 36 months of age. Menstrual bleeding was monitored and ovulation was inferred from a sustained rise in serum progesterone. In order to assess the sensitivity of luteinizing hormone-releasing hormone (LHRH) neurons to excitation, the response of serum LH to the acute administration of the glutamate receptor agonist N-methyl-, -aspartic acid (NMDA) was assessed prior to menarche, 2 months following menarche, and during the follicular phase of a female's third ovulation or 50 days after a female's first ovulation. In addition, the pituitary response of LH secretion to an LHRH agonist was assessed during the follicular phase of a female's fourth ovulation or 75 days following her first ovulation.IGF-I treatment effectively elevated serum concentrations by more than 86% of the values observed in Con animals. Although the treatment also enhanced the developmental increase in IGF binding protein-3 (IGFBP-3), IGF-I was increased proportionately more, resulting in a significantly higher molar ratio of IGF-I:IGFBP-3 in treated females throughout the course of the study. Treatment with IGF-I did not affect age at menarche but did significantly advance the age of first ovulation.Consequently, the interval between menarche and first ovulation was significantly shorter in Igf compared with Con females. Although the total number of ovulations exhibited by Igf (3·8 0·3) and Con females (3·0 0·5) in the 12 months following menarche was similar, significantly more of these were characterized by normal luteal phase progesterone secretion in Igf (100% 0) compared with Con females (64% 17). An analysis of cycles with a normal luteal phase revealed that serum estradiol during the luteal phase was significantly higher in Igf compared with Con females. Finally, IGF-treated females responded to NMDA treatment with a significantly greater increase in serum LH following menarche but not prior to menarche. In contrast, the response of serum LH to an LHRH agonist did not differ between Igf and Con females.These data suggest that the premature elevation in IGF-I levels, and consequently the ratio of IGF-I:IGFBP-3, accelerates the tempo of the final stages of puberty in rhesus monkeys. This action of IGF-I is probably the result of an increase in LHRH neuronal activity and is not due to a change in pituitary sensitivity to LHRH stimulation. In addition, ovarian sensitivity to LH stimulation during the luteal phase is also increased by IGF-I. Taken together, these data suggest that developmental increases in peripheral IGF-I secretion participate in the neuroendocrine regulation of puberty in...

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“…We reported recently that alteration of the GABAergic system by sodium valproate had no significant effect on pulsatile LH secretion by normal women during the late follicular phase (22) and mid-late luteal phase (23). However, the findings in rats that the rise in serum LH concentration following ovariectomy is associated with a fall in hypothalamic GABA levels, and that the fall in serum LH concentration following administration of estradiol is associated with an increase in hypothalamic GABA levels (7,24), suggest that GABAergic regulation of LH secretion may depend on steroid levels (25,26). If so, the absence of any significant change in LH secretion following valproate administration in our study of normal women may have been due to the high estradiol and progesterone levels of our subjects, which may have ensured that their basal GABA levels were already high enough to produce the maximum possible effect of GABA on LH secretion (27).…”

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confidence: 78%

Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women

Lado-Abeal¹,

Liz²,

Rey

et al. 1996

European Journal of Endocrinology

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It is well established that valproate increases hypothalamic concentrations of gamma-aminobutyric acid (GABA). Although little research has been done on the role of GABA in the control of pulsatile luteinizing hormone (LH) secretion in humans, our group recently found that administration of valproate had no significant effect on pulsatile LH secretion in late follicular and mid-late luteal phase normal women. However, the results of several studies of rats suggest that GABAergic regulation of LH secretion may depend on steroid levels. The objective of this work was to determine whether regular administration of sodium valproate inhibits pulsatile LH secretion in ovariectomized women. Twelve women who had undergone ovariectomy for causes other than malignant tumors were each studied in two 8 h sessions, in each of which blood samples were taken every 5 min. The first session was the control; for the second. 400 mg of sodium valproate was administered every 8 h during the seven preceding days and at 08.00 h and 14.00 h on the day of the study session. Serum valproate was determined by repolarization fluorescence spectrophotometry, and LH, estradiol and progesterone by radioimmunoassay. The serum LH series were subjected to a deconvolution procedure to reconstruct the pattern of pituitary LH secretion. Luteinizing hormone pulses were identified by the authors' non-parametric method. Control and post-valproate results were compared with regard to number of pulses, pulse duration, the quantity of LH secreted in each pulse, interpulse interval and mean serum LH level. There was no statistically significant difference between control and post-valproate results for any of the variables considered. It is concluded that sustained serum valproate levels do not alter pulsatile secretion of LH in ovariectomized women. This implies that, in humans, GABA is probably not a decisive factor in the regulation of the GnRH pulse generator.

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GABA control of LHRH release is dependent on the steroid milieu

Cited by 9 publications

References 24 publications

Changes of Expression of Genes Related to the Activity of the Gonadotrophin‐Releasing Hormone Pulse Generator in Young Versus Middle‐Aged Male Rats

Changes of Expression of Genes Related to the Activity of the Gonadotrophin‐Releasing Hormone Pulse Generator in Young Versus Middle‐Aged Male Rats

Premature elevation in serum insulin-like growth factor-I advances first ovulation in rhesus monkeys

Effects of valproate-induced alteration of the GABAergic system on pulsatile luteinizing hormone secretion in ovariectomized women

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