Regulation of the hypothalamic corticotropin-releasing hormone neurosecretory system

It is unequivocal that prolactin is an influential hormone in murine mammary tumorigenesis The Berenblum hypothesis (7), a well-known theoretical model of tumorigenesis that depicts this oncogenic process as a two-step mechanism, ie, initiation and promotion, is a conceptual scheme in which the action of prolactin in mammary tumorigenesis may be understood According to this conceptual model, prolactin would participate in both the initiation and promotion steps of mammary tumorigenesis, In the initiation phase, variations in prolactin secretion appear to influence the metabolism of the mammary epithelium, so that the epithelium would be either more receptive to or refractory to an initiating agent (eg, chemical carcinogen, physical carcinogens, oncogenic viruses, ets) ie, a permissive action In the promotion phase, prolactin may act as either a promoter or an antipromoter of the "transformed" mammary epithelium In promotion, the hormone may either directly or indirectly (via the ovary) stimulate mitotic activity of the "transformed" epithelium In antipromotion the hormone, in the presence of requisite hormones (eg, glucocorticoids), may synergistically induce differentiation (eg, lactation) in the "transformed" epithelium A tumor would result in the former (promotion) but not in the latter (antipromotion) case Whether or not prolactin is significantly influential in human breast tumorigenesis remains to be determined This is an extremely important area of research which is justifiably receiving increased attention For if prolactin can be shown to influence human breast epithelium in a manner similar to its effect on rodent mammary tissue, then prophylactic and/of chemotherapeutic control of human breast tumorigenesis may be feasible by appropriate drug-mediated prolactin suppression

https://cancerres.aacrjournals.org/content/canres/37/4/951.full.pdf

Prolactin and Murine Mammary Tumorigenesis: A Review

An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or...

https://www.nejm.org/doi/pdf/10.1056/NEJM197703172961103?listPDF=true

Galactorrhea: A Study of 235 Cases, Including 48 with Pituitary Tumors

Dopaminergic receptors in the anterior pituitary gland. Correlation of [3H]dihydroergocryptine binding with the dopaminergic control of prolactin release.

Since the isolation of the enkephalins five yr ago, there has been an explosive increase in knowledge concerning the effects of the opiates and opioid peptides. This review deals with the interactions of opiates with the endocrine system in rat and man. The opioid peptides have been demonstrated to exert a variety of effects on pituitary hormone secretion in rat and man. In the rat, opiates stimulate growth hormone, prolactin and ACTH release and inhibit the release of the glycoprotein hormones. In man, the physiologic role of the endogenous opiates appears to be involved predominantly in ACTH and gonadotrophin regulation. Opiate effects are mainly exerted at the level of the hypothalamus but further modulating effects may occur at the pituitary and at end-organs. Opiate-induced hormonal effects appear to be mediated through dopaminergic and/or serotonergic mechanisms. Recent studies have also suggested a possible local neuromodulatory role for the opioid peptides in the control of carbohydrate metabolism and reproductive processes.

The endocrinology of the opiates and opioid peptides

A single dose of 2 Bro-α-ergocryptine (CB-154) lowers serum prolactin for at least 12 hrs. in normal subjects. CB-154 in the immediate postpartum period causes a marked suppression of the elevated serum prolactin levels and completely inhibits puerperal lactation and breast engorgement. In patients with galactorrhea and elevated serum prolactin values the ergot alkaloid effectively lowers serum prolactin concentrations leading to a cessation of the galactorrhea.

THE INHIBITION OF PROLACTIN SECRETION IN MAN BY CB-154 (2-Br-α-ergocryptine)

Nine female patients with galactorrhea were selected for treatment with Bromocriptin® (CB-154), a specific inhibitor of prolactin secretion. Elevated plasma prolactin (hPRL) was found in 7 of these cases, whereas 2 exhibited values within normal limits. LHRH (100 μg) stimulation elicited plasma LH/FSH increases in 6 of the women who were amenorrheic prior to therapy, indicating a suprasellar cause for the patients' failure to cycle. After TRH (250 μg) stimulation, 5 women out of 6 exhibited a blunted hPRL response and 4 of them failed to show any elevations after administration of chlorpromazine. It was only in one patient who exhibited basal hPRL within the normal range, that an average response to TRH was elicited. The possible mechanisms explaining the low levels of pituitary stimulation obtained are discussed. Treatment with CB-154 (3–5 mg/day) induced a fall in serum hPRL accompanied by cessation of milk secretion in 8 patients. Menses were restored in 7 amenorrheic women and corpora lutea f...

Clinical and hormonal response to bromocriptin (CB-154) in the galactorrhea syndromes.

Prolactin and deficient luteal function

The antigalaclic action of Br-ergocryptine (CB 154 was studied in a group of women in the postpartum period who were compared with another two groups of normal breast-feeding mothers and estrogen-treated women. Treatment with Br-ergocryptine induced a fall in blood prolaclin concentrations to below the basal values found in nonlactaling women. No milk secretion was recorded in this group. This compound also inhibited the prolactin peak that normally occurs in response to suckling. Lactation suppression was also effective once it had been initiated, regardless of the prolactin concentrations at the time therapy was started. Inhibition of milk secretion by Brergocrypline also was observed in 2 women at a time when serum prolactin had reached normal levels and despite breast stimulation. Since treatment depressed serum prolactin values even further, it cannot be clearly explained whether the antigalaclic action was due simply to the fall in serum prolactin concentrations to a level below the normal range or to the abolition of the postsuction response. Exogenous administration of estrogen failed to inhibit prolactin secretion but was effective in suppressing lactation, thus suggesting a peripheral action on the mammary gland

E. del Pozo

Papers

THE INHIBITION OF PROLACTIN SECRETION IN MAN BY CB-154 (2-Br-α-ergocryptine)

Clinical and hormonal response to bromocriptin (CB-154) in the galactorrhea syndromes.

Prolactin and deficient luteal function

Prolactin inhibition and suppression of puerperal lactation by a br-ergocryptine (cb 154)

Prolactin inhibition and suppression of puerperal lactation by a Br-erocryptine (CB 154). A comparison with estrogen