Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

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Prolactin: Structure, Function, and Regulation of Secretion

The Dopamine Hypothesis of Schizophrenia: A Review*

THE TONIC and cyclic secretion of gonadotropins is mediated by the hypothalamic production of gonadotropin releasing hormone (GnRH). The direct assessment of hypothalamic function has been hampered by the absence of reliable methods for the measurement of GnRH production and secretion. Endogenous hypothalamic GnRH probably never reaches the general circulation in sufficiently high concentration to be measured by RIA (1–5), since the pituitary gland has the capacity to metabolize the majority of the peptide secreted into the hypothalamo-hypophyseal portal circulation (6–10). Attempts to determine the rate and amplitude of GnRH secretion have shown that GnRH concentrations in hypophyseal stalk plasma fluctuate between 20 and 800 pM (11–14). Such studies have revealed that GnRH is released in a pulsatile fashion, although rapid changes in secretion rate cannot be detected during the long period required for sample collection. In addition to modulating the concentration of GnRH in hypophyseal portal plasma (1...

Gonadotropin-Releasing Hormone Receptors: Characterization, Physiological Regulation, and Relationship to Reproductive Function

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

Dopamine and sexual behavior.

A single intravenous injection of tryptophane, 5-hydroxytryptophane, serotonin or melatonin was given to rats on the morning of proestrus and to hypophysectomized, pituitarygrafted female rats. The 5-hydroxytryptophane increased serum prolactin about 9 fold by 30 min after injection and about 6 fold by 1 hr after injection as compared to control values; it also doubled serum prolactin values in hypophysectomized rats with an anterior pituitary graft. Tryptophane approximately doubled serum prolactin over control values by 30 min and 2 hr after injection, but these differences were not significant statistically. Serotonin itself did not significantly alter serum prolactin levels, but melatonin significantly increased serum prolactin over control levels by 1 and 2 hr after injection. These results suggest that brain serotonin, its precursors and melatonin may have a role in stimulating prolactin release, and thereby serve to counter the inhibitory effects of hypothalamic catecholamines on prolactin release....

Effects of Serotonin Precursors and Melatonin on Serum Prolactin Release in Rats

The effects of ergocornine, estradiol benzoate (EB) or both on anterior pituitary (AP) and serum prolactin concentrations were studied in ovariectomized or hypophysectomized rats with a pituitary transplant, and directly on the AP in vitro. Injections of 5 or 10 μg EB into ovariectomized rats for 5 days produced 3-to 4-fold increase in AP prolactin concentration, a 6-to 8-fold rise in serum prolactin and increases in pituitary weight and mammary growth. Doses of 0.1 or 0.3 mg ergocornine methanesulfonate (ERG) partially or completely inhibited the stimulatory effects of EB on each of these parameters. Transplantation of one AP into the kidney capsule of hypophysectomizedovariectomized rats resulted in relatively high blood prolactin levels. ERG reduced prolactin release from the AP graft and mammary growth, whereas EB increased both AP and serum prolactin concentrations and mammary growth. When given together, ERG partially counteracted EB stimulation of pituitary and serum prolactin levels and mammary gr...

Direct Inhibition by Ergocornine of Pituitary Prolactin Release

A single intraperitoneal injection of reserpine (R), chlorpromazine (C), alphamethyl- para-tyrosine (AMPT) or alpha-methylmeta-tyrosine (AMMT) in proestrous rats produced profound elevations in serum prolactin 30 min to 4 hr after injection. R, C and AMPT decreased pituitary prolactin concentration, whereas AMMT increased it. This indicates that these 4 drugs evoked rapid release of prolactin from the pituitary, and that AMMT also elicited rapid synthesis of prolactin. The increased release of pituitary prolactin may be related to inhibition by the drugs of catecholamine activity in the hypothalamus and/or to reduced hypothalamic PIF content. A single intraperitoneal injection of dopamine (D), epinephrine (E), norepinephrine (NE) or serotonin (S) had no significant effect on serum prolactin levels 1 or 2 hr after injection. D, E and NE also had no effect on serum prolactin values when injected intracarotidly. The higher doses of E and D but not NE produced a small decrease in pituitary prolactin concentra...

Effects of Central Acting Drugs on Serum and Pituitary Prolactin Levels in Rats

The in vitro effects of epinephrine, norepinephrine and dopamine on prolactin release by the rat pituitary were studied in a 4-hr incubation system. The addition of 10 or 20 ng of epinephrine or norepinephrine to 1 ml of a physiological medium containing ½ male rat pituitary significantly increased prolactin release, whereas doses of 200–1000 ng markedly inhibited prolactin release. Incorporation of 2–40 ng of dopamine into the medium had no effect, whereas 80–640 ng significantly decreased prolactin release. These results indicate that the effects of catecholamines on pituitary prolactin release in vitro are dose dependent. (Endocrinology 87: 673, 1970)

Biphasic effects of catecholamines on pituitary prolactin release in vitro.

SummaryA single intraperitoneal injection of L-dopa, the precursor of dopamine, into female rats significantly reduced serum prolactin concentration at 30 min, 1 hr, and 2 hr after injection compared to pretreatment levels or control rats not given this drug. A single injection of each of 3 monoamine oxidase inhibitors, pargyline, iproniazid or Lilly-15641, also significantly decreased serum prolactin below pretreatment values. Injection of L-dopa and pargyline together was more effective than either alone in lowering serum prolactin. Each of the above drugs is believed to reduce pituitary prolactin release because it increases catecholamine activity in the hypothalamus. By contrast, a single injection of methyldopa, which inhibits catecholamine synthesis, increased serum prolactin many fold over pretreatment levels. A single injection of d-amphetamine, a sympatheticomimetic drug, also greatly increased serum prolactin concentration.AddendumThe hypothalami of the rats treated with saline (controls), ipron...

Kuew-Hsiung Lu

Papers

Effects of Serotonin Precursors and Melatonin on Serum Prolactin Release in Rats

Direct Inhibition by Ergocornine of Pituitary Prolactin Release

Effects of Central Acting Drugs on Serum and Pituitary Prolactin Levels in Rats

Biphasic effects of catecholamines on pituitary prolactin release in vitro.

Inhibition by L-Dopa and Monoamine Oxidase Inhibitors of Pituitary Prolactin Release; Stimulation by Methyldopa and d-Amphetamine