Zsuzsanna Ács

Role of hypothalamic factors (growth-hormone-releasing hormone and gamma-aminobutyric acid) in the regulation of growth hormone secretion in the neonatal and adult rat.

N-methyl aspartic acid (NMA) was without effect on the pituitary growth hormone (GH) secretion of adult and neonatal rats in vitro. Administration of NMA resulted in a rapid rise of plasma GH levels in intact but not in arcuate-nucleus-lesioned adult rats, indicating that NMA stimulated GH-releasing hormone (GRH) secretion. In 2-day-old rats, both NMA and gamma-aminobutyric acid (GABA) elevated plasma GH levels in a dose-related fashion; GRH administration was without effect. The elevation of plasma GH levels after NMA injection was reduced by administering an antibody to GRH. These results indicate that GH secretion is partly regulated by endogenous GRH in the newborn rat but that the elevation of plasma GH levels after GABA is not mediated by GRH. The high plasma GH levels seen in the newborn rat may result from the independent action of GABA and GRH but the effect of other factors cannot be excluded either.

Site of γ-Aminobutyric Acid (GABA)-Mediated Inhibition of Growth Hormone Secretion in the Rat

The effect of altering γ-aminobutyric acid (GABA) activity on growth hormone (GH) secretion of freely moving chronically cannulated male rats was studied. Systemic injection of the GABA agonist muscim

Growth hormone secretion of the neonatal rat pituitaries is stimulated by gamma-aminobutyric acid in vitro.

Growth hormone secretion from pituitaries of neonatal rats was stimulated by gamma-aminobutyric acid (GABA) and the GABA agonist muscimol in vitro. This response to GABA was absent after the 9th postnatal day. The stimulation of growth hormone secretion by GABA was antagonized by bicuculline-methiodide and by picrotoxin. Diazepam stimulated while baclophen had no effect on growth hormone secretion. This stimulatory GABA effect might be related to a certain developmental stage of the pituitary GABA receptors or to the lack of hypothalamic regulatory influence(s) in the newborn.

Gamma-Aminobutyric Acid-Induced Elevation of Intracellular Calcium Concentration in Pituitary Cells of Neonatal Rats

Gamma-aminobutyric acid (GABA) increased intracellular calcium concentration ([Ca2+]i) of newborn rat pituitary cells in suspension measured by the FURA-2 method. The effect of GABA was dose dependent in the range of 0.1-10 microM. This effect diminished with postnatal age as measured at days 2, 14 and 21, and in adult animals. The GABA stimulation was mimicked by muscimol; in contrast, baclofen (up to 100 microM) was ineffective. Picrotoxin, a GABAA antagonist interacting with GABA-activated chloride ionophores, caused a dose-dependent inhibition of the [Ca2+]i elevating effect of 100 microM GABA or muscimol. These observations indicate the involvement of GABAA type receptors. The GABA or muscimol effect on [Ca2+]i was antagonized by nifedipine (10 microM) or verapamil (50 microM), and completely abolished in the presence of 4 mM EGTA (low-calcium medium). The findings indicate the presence of depolarizing GABAA receptors on neonatal rat pituitary cells. It seems very likely that the mechanism by which GABA receptor occupation results in elevated [Ca2+]i is a membrane depolarization by increased Cl- conductance followed by calcium influx through L-type voltage-dependent calcium channels.

Effect of cortexolone on the feedback action of dexamethasone

Cortexolone in a dose of 1 mg/100 g body wt., administered to rats prior to dexamethasone, prevented dexamethasone from suppressing stress-induced ACTH-release without interfering with the effect of dexamethasone on the resting plasma corticosterone level.

Monosodium glutamate lesions inhibit the N-methyl-D-aspartate-induced growth hormone but not prolactin release in rats

Large doses of glutamate administered to newborn rats damage permanently the neurones in the hypothalamic arcuate nucleus containing the growth hormone releasing hormone and the prolactin inhibiting dopamine neuron cell bodies. Since adult animals that underwent neonatal glutamate treatment still have a relatively well functioning growth hormone and prolactin system, we tested whether in the adults the excitatory amino acid sensibility is changed. After i.v. injection of different doses (10 or 30 mg/kg) of N-methyl-D-aspartate (excitatory amino acid receptor subtype agonist) growth hormone levels were significantly increased in the control groups but there was no rise in neonatally glutamate treated male and female rats. The level of prolactin was increased by N-methyl-D-aspartate, too, but the glutamate treatment had no effect on the rise. Our study suggests that systemic administration of N-methyl-D-aspartate increases plasma growth hormone level by activating the growth hormone releasing cells in the arcuate nucleus, but the intact tuberoinfundibular dopaminergic pathway is not essential for its prolactin stimulatory effect.

Significance of chloride channel activation in the gamma-aminobutyric acid induced growth hormone secretion in the neonatal rat pituitary

Growth hormone (GH) secretion of the neonatal pituitary is stimulated by tau-aminobutyric acid (GABA) (1,2). Since in most cases GABA is known to act by increasing postsynaptic membrane permeability to chloride ions we tested the importance of chloride channel activation in the GH stimulatory effect of GABA in the neonatal pituitary. In the absence of chloride in the superfusion medium GABA was without effect on GH secretion of the neonatal pituitaries and its effect was attenuated by chloride channel inhibitors. The effect of growth hormone releasing hormone (GHRH) on GH secretion was attenuated in the chloride-free media, but it was not affected by simultaneous administration of chloride channel blockers. The present study indicates that GH stimulatory effect of GABA in the neonatal pituitaries might involve chloride channel activation probably resulting in secondary activation of calcium channels.

Corticotroph, somatotroph and mammotroph cell kinetics in the postnatal infant female rat

The aim of this work was to detect if hypothalamic-pituitary maturation was accompanied by significant proliferation changes in differentiated pituitary cell pools. For this purpose, pituitary corticotroph (Ct), mammotroph (Mt) and somatotroph (St) proliferation activities were scanned in intact female rats during the postnatal (P) period (1–35 postnatal days). The techniques of tritiated thymidine labelling, immunostaining and autoradiography were combined to visualize DNA synthesis of hormone containing cells. Immunoreactive cell densities were measured using image analysis, and double labelled cells were counted. Corticotroph proliferation activity increased significantly on day P12, followed by an increase in the Ct proportion on days P13–14. This is the first observation of a spontaneous change of corticotroph proliferation at the end of the stress nonresponsive period. The mammotroph density and proliferation rate increased gradually during postnatal maturation, until the Mt pool overran other cell types of the female hypophysis on day 35. The somatotroph pool was the most numerous until day P20; the proliferation rate remained constant while St proportions increased reaching a plateau between days P13 and 20, then decreased to the adult level. Each cell type examined showed a characteristic, individual density and proliferation pattern.

Rat milk stimulates pituitary growth hormone secretion of neonatal pituitaries in vitro

Aqueous extracts of rat milk stimulated growth hormone (GH) secretion from superfused pituitaries of two-day old rats. The GH stimulatory effect of milk increased with the time elapsed postpartum; growth hormone releasing hormone and thyrotropin releasing hormone seem to be the major milk borne GH releasing factors. These results indicate that milk intake may play a role in maintaining the high plasma GH levels observed in the neonatal period.

Prolactin-synthesizing and prolactin-releasing activity of fetal and early postnatal rat pituitaries: In vivo and in vitro studies using RIA, reverse hemolytic plaque assay and immunocytochemistry

In vivo and in vitro prolactin (PRL)-synthesizing and PRL-releasing activity of fetal (days 12-22) and early postnatal (days 1-10 after birth) rat pituitaries were studied by means of radioimmunoassay (RIA), reverse hemolytic plaque assay and immunocytochemistry. Using RIA, PRL could first be detected, both in the pituitary and in the serum, on day 17 of fetal development. From this day on, pituitary PRL gradually increased, the rise was particularly marked during the postnatal period and became depressed for the first 10 days of postnatal life. On fetal day 18, 12-15% of monodispersed pituitary cells displayed PRL immunopositivity, but only 3-5% of PRL-positive cells were plaque-forming, i.e. released PRL. By the end of gestation 19-25% and on postnatal day 10 42-45% of all pituitary cells were PRL cells and 31-35 and 15-17% of PRL-positive cells, respectively released PRL. Both pre- and postnatal PRL cells in monolayers were insensitive to TRH treatment. Pituitary primordia immunocytochemically and radioimmunologically negative for PRL (13- to 14-day-old fetal) when placed in serum-free organ culture were able to synthesize and release PRL. Fetal pituitary exhibited a highly regular increasing pattern of daily PRL release during a 7-day-culture period. Data obtained both in vivo and in vitro did not exhibit any sex differences. The present findings are consistent with all those observations suggesting an early emergence of fetal rat pituitary lactotrophs. The in vitro results support the concept that Rathkes pouch cells have substantial degree of independence from extrapituitary regulatory actions in the expression and further progression of specific functions.(ABSTRACT TRUNCATED AT 250 WORDS)