The role of gamma-aminobutyric acid (GABA) in the regulation of gonadotropin secretion in renal failure, was studied in 5 patients with chronic renal failure who were on maintenance dialysis. Di-n-propylacetic acid (valproic acid-VA), a GABA-transaminase inhibitor which has been shown to increase brain GABA levels, was used in the study.
VA produced no significant change in the basal serum LH and FSH concentrations, or in E2 or T concentrations in the renal failure patients, or the E2 and P concentrations in normal controls, but augmented the Δ LH (maximum increment above baseline) and Δ FSH response to LHRH. Δ LH rose from 30.4 ± 12.7 mlU/ml () to 41.1 ± 16.8 mlU/ml (p < 0.01) after VA, while Δ FSH rose from 2.8 ± 1.8 mlU/ml to 3.8 ± 1.6 mlU/ml (p < 0.05). The findings support a modulatory role for GABA in gonadotropin secretion in chronic renal failure.
PorterJ.C., NanselD.D., GudelskyG.A., ForemanM.M., PilotteN.S., ParkerC.R.Jr., BurrowsG.H., BatesG.W., MaddenJ.D.: Neuroendocrine control of gonadotropin secretion. Fed. Proc.39: 2896–2901, 1980.
2.
JuddS.J., RakoffJ.S., YenS.S.: Inhibition of gonadotrophin and prolactin release by dopamine: effect of endogenous estradiol levels. J. Clin. Endocrinol. Metab.47: 494–498, 1978.
3.
PorterJ.C., Ben-JonathanN., OliverC., EskayR.L., WintersA.J.: In Neuroendocrine Regulation of Fertility.Anand-KumarT.C. (Ed.), Karger, Basel, pp. 71–79, 1976.
4.
SawyerC.H.: Some recent developments in brain-pituitary ovarian physiology. Neuroendocrinology17: 97–124, 1975.
5.
KriegR.J., SawyerC.H.: Effects of intraventricular catecholamines on luteinizing hormone release in ovariectomized steroid-primed rats. Endocrinology99: 411–419, 1976.
6.
McCannS.M., MossR.L.: Putative neutrotransmitters involved in discharging gonadotropin-releasing neurohormone and the action of LH-releasing hormone on the CNS. Life Sci16: 833–852, 1976.
KouluM., LammintaustaR., KangasL., DahlstromS.: The effect of methysergide, pimozide and sodium valproate on the diazepam-stimulated growth hormone secretion in man. J. Clin. Endocrinol. Metab.48: 119–122, 1979.
9.
EliasA.N., GwinupG., ValentaL.J.: Effects of hydrocortisone, naloxone and valproic acid in patients with Nelson's syndrome and Cushing's disease. Clin. Endocrinology15: 151–154, 1981.
10.
EliasA.N., GwinupG.: Sodium valproate and Nelson's syndrome. Lancet1: 252, 1981.
11.
EliasA.N., ValentaL.J., Szekeres, GrossmanM.K.: Effect of di-n-propylacetic acid (valproic acid) on the TSH response to TRH. A presumptive role for gamma-aminobutyric acid. Metabolism30: 1021–1023, 1981.
12.
LimV.S., FangV.S.: Gonadal dysfunction in uremic men. A study of the hypothalamo-pituitary testicular axis before and after renal transplantation. Am. J. Med.58: 655–662, 1975.
13.
DistillerL.A., MorleyJ.E., SagelJ., PokroyM., RabinR.: Pituitary gonadal function in chronic renal failure: the effect of luteinizing hormone-releasing hormone and the influence of dialysis. Metabolism24: 711–20, 1975.
McCannS.M., VijayanE., Negro-VilarA.: The role of gamma-aminobutyric acid in control of anterior pituitary hormone release. Adv. Biochem. Psychopharmacol.20: 237–246, 1980.
16.
GrandisonL.: Anterior pituitary GABA receptors and their regulation of prolactin secretion. Adv. Biochem. Psychopharmacol.20: 219–227, 1980.
17.
VijayanE., McCannS.M.: The effect of intraventricular injection of gamma-aminobutyric acid (GABA) on prolactin and gonadotropin release. Brain. Res.155: 35–43, 1978.
18.
VijayanE., McCannS.M.: Blockage of dopamine (DA) receptors with pimozide and pituitary hormone release in response to intraventricular injection of gamma-aminobutyric acid (GABA) in conscious ovariectomized rats. Brain. Res.163: 69–76, 1979.
19.
YenS.S.C.: The human menstrual cycle. In Reproductive Endocrinology.YenS.S.C., JaffeR.B. (Eds.), W.B. Saunders Company, Philadelphia pp. 126–151, 1978.
20.
StoneS.C., JaramilloF., KastinA.J., ArimuraA., VargasJ.R., SchallyA.V., DickeyR.P.: Effect of LHRH on antibody formation, sperm count and plasma levels of gonadotropins and testosterone in normal men. Int. J. Fertil.19: 192–196, 1974.
21.
StoneS.C., DickeyR.P., KastinA.J., SchallyA.V.: LHRH and steroid levels in normal ovulatory women. Obstet. Gyn.48: 146–149, 1976.
