The role of the dopaminergic mechanism in the regulation of pituitary hormone secretion in women (author's transl)

Abstract

Although the tuberoinfundibular dopamine (DA) system has been well documented to play a role in the regulation of prolactin (PRL) secretion, conflicting data have been presented regarding the other pituitary hormones, especially with regard to gonadotropin and growth hormone (GH) secretion. The site of DA action on gonadotropin secretion also remains obscure. The purpose of the present study was to investigate the effect and site of action of DA and, in addition, to examine the effect of a DA receptor antagonist, metoclopramide (MCP), on pituitary LH, FSH, PRL and GH secretion in women.Dopamine HCl diluted in normal saline was infused at a rate of 4μg/kg/min for 180 min to 6 bilaterally ovariectomized women and 6 women with hyperprolactinemic amenorrhea (H-A). LH-RH (100μg) and TRH (500μg) were administered intravenously one month before and during the DA infusion (4μg/kg/min for 240 min, LH-RH and TRH being injected at 120 min) to 5 agonadal women. MCP (10mg) was injected intravenously to 5 agonadal women and 5 women with H-A. Blood samples were obtained through an indwelling venous catheter at 20 min intervals during the experiments. Serum LH, FSH, PRL and GH were measured by a double antibody RIA. Statistical analyses were performed by Student's paired or unpaired t-tests, as appropriate.Serum LH levels significantly declined during the DA infusion and returned to basal level after the termination of infusion in both groups of subjects. The maximum decrement was about 9-fold greater in agonadal women than in women with H-A (19.5 ± 2.4 vs. 2.1 ± 0.5mIU/ml, p<0.001). FSH levels also significantly decreased during the DA infusion in each group, but the degree of decline in FSH was not so remarkable as in LH. A significant decrease and a significant rebound increase from baseline level in PRL were observed during the DA infusion and after the termination of infusion respectively in both groups, and the maximum decrement and maximum rebound increment were significantly greater in women with H-A than in agonadal women. That is to say that the basal LH, FSH and PRL levels were significantly correlated with the magnitude of decline in each hormone during the DA infusion, respectively (r= 0.837, p<0.001 for LH; r=0.794, p<0.01 for FSH; r= 0.917, p< 0.0001 for PRL). On the whole, DA failed to cause a consistent pattern of GH secretion in both groups, but it seemed likely that DA may exert a dual effect, such as stimulatory or inhibitory, on GH secretion according to its basal level. No significant changes occurred in LH and FSH responses to LH-RH during the DA infusion when compared with those to LH-RH alone in 5 agonadal women. In contrast, PRL response to TRH during the DA infusion was completely abolished and significantly different from that to TRH alone. MCP caused a rapid and remarkable rise (about 14-fold increase) in PRL levels in 5 agonadal women and, on the other hand, a transient and modest one (about 1.5-fold increase) in 5 women with H-A. A significant negative correlation between maximum increment following MCP injection and basal level in PRL was recognized in this experimental group (r=-0.886, p<0.001). In the other pituitary hormones, no observable changes, except for a transient but significant rise of LH in women with H-A, were produced by MCP administration.These results suggest that DA exerts an inhibitory effect on pituitary LH, FSH and PRL secretion in proportion to each basal level. Furthermore, DA appears to inhibit gonadotropin secretion via suppressing LH-RH release, probably at the median eminence and to inhibit PRL secretion by a direct action on the anterior pituitary, because pituitary gonadotropin response to LH-RH was not altered even in the presence of DA, whereas PRL response to TRH was completely abolished by DA, and both the median eminence and anterior pituitary lie outside the blood-brain barrier,