Reexamination of dopamine as the prolactin-release inhibiting factor (PIF): supplementary agent may be required for dopamine to function as the physiological PIF.

A large number of studies have been performed concerning dopamine's inhibitory effect on prolactin release, but many of these studies have examined the effect of dopamine dissolved in a solution containing ascorbic acid. Ascorbic acid, routinely used to protect dopamine from oxidation, alone does not stimulate or inhibit prolactin release, but it can potentiate the inhibitory effect of dopamine in a static monolayer culture system by approximately 100 times. We have closely examined the inhibitory effect of dopamine on prolactin release in the absence of ascorbic acid using a perifusion system. Male rat adenohypophyses were dispersed with trypsin and cultured in a Petri dish to form cell clusters. Inhibition of prolactin release by dopamine (1 mumol/L) in the absence of ascorbic acid was sustained for only 63 min during the 2-h perifusion period. Following a 2-h period of incubation of dopamine in the same experimental solution, the dopamine concentration was reduced from 1 to 0.18 mumol/L, yet this "2-h-old dopamine" was still effective in inhibiting prolactin release (approximately 30 min). This result suggests that the lactotrophs may be desensitized by chronic exposure to a high concentration of dopamine in the absence of ascorbic acid. In contrast, when a low concentration of dopamine (3 nmol/L) containing ascorbic acid (0.1 mmol/L) was perifused, inhibition of prolactin release was sustained for the entire 2-h perifusion period. Although there may be a large number of explanations for dopamine's transient inhibitory effect on prolactin release, the present results suggest that dopamine may require supplementary agent(s) to effectively inhibit prolactin release and thus function as the prolactin release inhibitory factor (PIF).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiological evidence for a sex difference in neural regulation of prolactin secretion in rats.

Prolactin (PRL) secretion patterns were determined in freely moving male and female rats chronically fitted with electrodes in the sexually dimorphic component of the medial preoptic area (MPOA) and the median eminence (ME), together with a chronic atrial blood sampling catheter. Electrodes made of stainless steel or platinum-iridium were implanted bilaterally. Female rats with 4 electrodes in the ME exhibited an attenuated surge of PRL secretion on proestrus (injured group), rats with 2 electrodes in the ME had a normal proestrous surge (intact group). Basal PRL levels were not different between the two groups. Stimulation (100-Hz voltage pulses, 0.2 ms width, 10 s on/5 s off, total duration 25 min) did not produce lesions. Evidence is presented that experimentation was performed without stress. Electrical stimulation applied to the MPOA increased PRL secretion in males, decreased PRL secretion in proestrous females and was without effect in conscious or anesthetized diestrous females. Electrical stimulation applied to different locations of the ME was without effect in male and diestrous female rats; it reduced PRL secretion in proestrous females. These data demonstrate that the MPOA has a sexually differentiated function in the regulation of PRL secretion. The data do not provide evidence for a sexual dimorphism in prolactin-inhibiting factor and prolactin-releasing factor activity in the ME.

A prolactin-inhibiting factor within the precursor for human gonadotropin-releasing hormone.

The cloned complementary DNA sequence encoding the human gonadotropin-releasing hormone (GnRH) precursor protein was used to construct an expression vector for the bacterial synthesis of the 56-amino acid GnRH-associated peptide (GAP). GAP was found to be a potent inhibitor of prolactin secretion and to stimulate the release of gonadotropins in rat pituitary cell cultures. Active immunization with peptides corresponding to GAP sequences led to greatly increased prolactin secretion in rabbits.

[Current knowledge on the biochemistry and function of hypothalamic hormones]. / Neuere Erkenntnisse zur Biochemie und Funktion der Hypothalamushormone.

By specialized cell types of the hypothalamus 6 peptides (liberins) acting stimulating on the synthesis and secretion of hormones of the pituitary gland and 3 peptides acting inhibiting (statins) were formed. The synthesis of the hypothalamus hormones apparently takes place from larger precursor molecules. Under influence of corticoliberin the pro-opiomelanocortin is formed in the pituitary gland, the breaking up of which produces in the anterior pituitary lobe the ACTH, the beta-lipotropin and the beta-endorphin as well as in the middle lobe above all melanotropins. The secretion of the growth hormone is furthered above all by the somatoliberin and inhibited by the somatostatin. The luliberin stimulates the secretion of follicle stimulating hormone (FSH) and the luteinising hormone (LH). In increased secretion of prolactin the supply of the FSH- and LH-synthetizing cells with receptors for the luliberin is decreased. The secretion of the prolactin is furthered by the prolactoliberin and inhibited by the prolactostatin. In the regulation of the release of the melanotropins also participate 2 peptides. In the adrenal cortex the melanotropins further the synthesis of glucocorticosteroids stimulated by ACTH.

Dopamine, PIF, and other regulators of prolactin secretion.

Considerable evidence now exists that dopamine is a physiological prolactin inhibiting factor (PIF); however, it may not represent the only PIF. Amphetamine, which releases newly synthesized dopamine and blocks prolactin release, caused an increased in dopamine levels in the pituitaryb gloand. Prolactin release appears to be regulated also by a prolactin releasing factor (PRF). A wide variety of hypothalamic peptides stimulate prolactin release, but only two of these (thyrotropin releasing hormone and vasoactive intestinal polypeptide) can act directly on the pituitary and thus are candidates for PRF.

Relation of the neuroendocrine system to the development and growth of experimental mammary tumors.

The regulation of hormonal influences on mammary tumor development and growth resides in the hypothalamus. The two major hormones essential for mammary tumor development in the rat and mouse, and also for mammary tumor growth in the rat, are prolactin and estrogen. Prolactin secretion is directly controlled by the hypothalamus, and estrogen indirectly via the pituitary gonadotropins. Treatments that increase prolactin secretion in the rat and mouse increase the incidence of spontaneous mammary tumors, whereas treatments that decrease prolactin or estrogen secretion decrease the incidence of spontaneous mammary tumors in these species. In carcinogen treated rats, either an increase or decrease in prolactin or ovarian hormones inhibits development of mammary cancers. After the appearance of mammary tumors in rats, spontaneous or carcinogen-induced, a reduction in prolactin results in reduced mammary tumor growth, and an increase in prolactin in enhanced mammary tumor growth. Either a reduction in estrogen or an excess of estrogen inhibits mammary tumor growth in rats. Large doses of estrogen inhibit mammary tumor growth by preventing prolactin from stimulating tumor growth. In mice with well established mammary tumors, prolactin or estrogen have relatively little effect since these tumors are largely autonomous.