Effect of Dopamine on the Biological Activity and in Vitro Release of ACTH and FSH

Abstract

Considerable evidence is accumulating suggesting that catecholamines play a role in the regulation of anterior pituitary hormone secretion. In addition to the widespread distribution of noradrenergic nerve terminals in the hypothalamus, there is a particularly prominent group of dopaminergic nerve endings in the median eminence ( 1 ) . Stressful stimuli, such as electric shock, hemorrhage, and hypoglycemia which stimulate ACTH secretion, cause a decrease in brain norepinephrine content ( 2), and norepinephrine turnover in hypothalamic nerve terminals is increased under the influence of immobilization stress (3). Furthermore, reserpine, a catecholamine-depleting agent, stimulates ACTH secretion (4), whereas, amphetamine, a catecholamine-releasing agent, inhibits ACTH secretion ( 5 ) .Alterations in hypothalamic catecholamines also appear to be correlated with changes in gonadotropin and prolactin secretion. Increased fluorescence of the dopaminergic fibers in the median eminence has been observed in pseudopregnant and lactating rats ( 1 ) . Castration of male and female rats, which increases FSH and LH secretion (6), results in altered ratios of hypothalamic content of norepinephrine and dopamine (7). Alterations in brain norepinephrine turnover have been reported in castrated male and female rats (8). Finally, drugs such as reserpine and a-methyltyrosine which are known to deplete brain catecholamines (9, 10) have been shown to delay the onset of puberty (1 l ) , inhibit ovulation (12, 13), induce pseu-dopregnancy ( 12), and cause increased prolactin secretion and lactation (14) in the female rat.There are several ways that brain monoamines may affect the secretion of anterior pituitary hormones. Possible mechanisms include serving as transmitters in neural pathways providing input to neurons secreting releasing factors; mediation of presynaptic inhibition on the terminals of such neurons; altering flow in the hypothalamic-hypophyseal portal blood vessels; or direct action on the anterior pituitary cells. This paper reports results of a series of experiments in which the possibility of a direct action of dopamine on the pituitary was tested by incubating anterior pituitary tissue with dopamine in vitro and measuring the amount of ACTH and FSH in the incubation medium.Methods. Anterior pituitary glands were obtained from 200-250 g male Sprague-Dawley rats (Berkeley Pacific Company) that were sacrificed by decapitation. Four halves of hemisected rat anterior pituitaries were preincubated in 2 5-ml Erlenmeyer flasks containing 3 ml of medium 199 for 20-30 min a t pH 7.4 and 37' under constant gassing with 95% 02-5% COz. This preincubation medium was then discarded, replaced by fresh medium, and the incubation was continued for 6 hr under identical conditions.

<i>In vitro</i> Release of ACTH from Dispersed Rat Pars Intermedia Cells. II. Effect of Neurotransmitter Substances

“…At lower concentrations, no altera tion in release was observed, but at the highest concentrations, all 3 sub stances inactivated ACTH (table I). Similar results have been reported in studies of ACTH release from the PD [Van Loon and Kragt, 1970]. It is not possible, in our experimental model, to define more clearly this effect of the 3 catecholamines on the release of ACTH from the PI (inactivation of ACTH or interference in the ACTH bioassay).…”

The Specificity of an Ovine Pituitary Incubation System Linked With Gonadotrophin Assays for Detecting Gonadotrophin Releasing Activity

“…Van Loon & Kragt (1970) found that dopamine denatured FSH in an in-vitro system, and Kamberi, Schneider & McCann (1970) recorded a slight decrease in FSH release at the highest dose of nor¬ adrenaline used in specificity studies with rat pituitary tissue in vitro. The dose used was approximately equivalent to half the dose used in the present experiments.…”

Azaperone, pimozide and bromocryptine and the stress response to transport in male goats: a preliminary study

“…Side-effects of the drugs could have been responsible and the situation may be resolved by counter-acting these by additional pharmacological means or by in vitro studies. It has been reported that dopamine did not alter basal or stimulated release of ACTH from pituitary tissue in vitro (Van Loon & Kragt, 1970), but those experiments were carried out under almost maximal stress load and with large amounts of catecholamines. Further in vitro studies may delineate the effects of dopamine at hypothalamic and pituitary levels.…”