Prolactin: Structure, Function, and Regulation of Secretion

Abstract

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.

Nalmefene Induced Elevation in Serum Prolactin in Normal Human Volunteers: Partial Kappa Opioid Agonist Activity?

“…As neither of these peptides has extensive penetrance across the blood-brain barrier, their effects are likely limited to TIDA as opposed to mesolimbic-mesocortical dopaminergic neurons. In humans, dopamine D2 receptors on anterior pituitary lactotrophs act through tonic inhibition from TIDA neurons as the principal modulator of peripheral prolactin release (Durham et al, 1996;Freeman et al, 2000). As kappa-opioid receptors present on presynaptic dopamine terminals and mu-opioid receptors present on GABAergic interneurons inhibit TIDA, serum prolactin also serves as a biomarker for kappa-and mu-opioid receptor agonist activity.…”

“…In humans, prolactin is secreted from the anterior pituitary and is primarily regulated through tonic inhibition by tuberoinfundibular dopaminergic (TIDA) neurons (Freeman et al, 2000). Dopamine from TIDA neurons acts at dopamine D2 receptors present on pituitary lactotrophs to inhibit prolactin release (Freeman et al, 2000).…”

“…Dopamine from TIDA neurons acts at dopamine D2 receptors present on pituitary lactotrophs to inhibit prolactin release (Freeman et al, 2000). The endogenous opioid system, more specifically mu-and kappa-opioid receptors localized on dopaminergic neurons within the mesolimbic-mesocortical and TIDA systems, modulates dopamine release.…”

Prolactin modulates phosphorylation, signaling and trafficking of epidermal growth factor receptor in human T47D breast cancer cells

“…It is also produced locally by multiple extrapituitary sites, including the mammary epithelium, placenta, uterus, bone, brain and immune system, and can act in an autocrine/ paracrine manner (Ben-Jonathan et al, 1996;Freeman et al, 2000). PRL stimulates normal mammary growth, development and lactation, but also affects other reproductive aspects,such as osmoregulation, stress and behavior (Horseman, 1999;Rui, 2000;Hovey et al, 2001;Goffin et al, 2002;Grimm et al, 2002).…”

Cocaine- and amphetamine-regulated transcript (CART) expression is differentially regulated in the hypothalamic paraventricular nucleus of lactating rats exposed to suckling or cold stimulation

“…Thus, the central actions of CART could have a dual regulatory action on prolactin secretion as a result of direct release into the portal system from hypophysiotropic PVN neurons and through effects on TIDA neurons. Dopamine released from the tuberoinfundibular dopaminergic neurons (TIDA) exerts a tonic inhibitory tone on prolactin secretion and factors that inhibit or stimulate their activity consequently stimulate or inhibit prolactin release (Freeman et al, 2000). CART terminals impinge on TIDA terminals and increase DA turnover leading to a decrease in serum prolactin (Yang and Shieh 2004).…”