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Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice

Published on Friday, 25 February 2022

Abstract

PRL and GH, along with placental lactogens (PLs), form a family of hormones that probably result from the duplication of an ancestral gene. It was early in the 20th century that changes in the histology of the anterior pituitary gland of pregnant women were first noted. French researchers were the first to identify a pituitary factor capable of inducing milk secretion in rabbits. American scientists made similar observations, and in addition to naming the new pituitary factor prolactin, showed that PRL was able to stimulate the growth of the pigeon crop sac. PRL has now been shown to exist in all vertebrates thus far examined.

Because human GH preparations were lactogenic in conventional bioassays, and because early attempts to separate GH and PRL activities failed, there was some question whether a separate PRL existed in humans. There was strong clinical and histological evidence to suggest that the two hormones were present in humans. Finally, human PRL (hPRL) was successfully isolated and purified, which led to numerous subsequent pathophysiological studies.

PRL has more actions than all other pituitary hormones combined. The initial step in the action of PRL, like all other hormones, is the binding to a specific membrane receptor, the PRL receptor (PRLR). Similar to the ligand, the PRLR has also been shown to be a member of the same family as the GH receptor and also part of the larger class of receptors, known as the class 1 cytokine receptor superfamily.

In this review we will briefly discuss the structure of PRL and its family members and the fact that PRL is produced at sites outside the pituitary gland (extrapituitary PRL), and thus may act as a hormone, by the classic endocrine pathway, and as a growth factor, neurotransmitter, or immunoregulator, in an autocrine-paracrine fashion. The structural organization of the PRLR and its complex binding and activation will be described, as well as the tissue distribution of the receptor. The original list of 85 different actions of PRL in vertebrates has been expanded to include more than 300 separate functions of this multifaceted hormone. The signal transduction mechanisms activated after the binding of PRL to the receptor will be described. Finally, the phenotypes associated with the knockout of the PRLR gene in mice will be reviewed. Although this approach does not apply to all reported functions of PRL (seasonal actions, species-specific effects, etc.), in many instances the knockout model is useful to identify actions directly associated with PRL or PL and, by comparison with other gene deletions, suggests which actions have been taken over by another hormone or cytokine.

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