Prolactin and the prolactin receptor: new targets of an old hormone

Abstract

Prolactin (PRL) is one of a family of related hormones including growth hormone (GH) and placental lactogen (PL) that are hypothesized to have arisen from a common ancestral gene about 500 million years ago. Over 300 different functions of PRL have been reported, highlighting the importance of this pituitary hormone. PRL is also synthesized by a number of extra-pituitary tissues including the mammary gland and the uterus. Most of PRL's actions are mediated by the unmodified 23 kDa peptide, however, PRL may be modified post-translation, thereby altering its biological effects. PRL exerts these effects by binding to its receptor, a member of the class I cytokine receptor super-family. This activates a number of signaling pathways resulting in the transcription of genes necessary for the tissue specific changes induced by PRL. Mouse knockout models of the major forms of the PRL receptor have confirmed the importance of PRLs role in reproduction. Further knockout models have provided insight into the importance of PRL signaling intermediates and the advent of transcript profiling has allowed the elucidation of a number of PRL target genes.

In vitro multipotent differentiation and barrier function of a human mammary epithelium

“…Although both ductal and alveolar cells express milk proteins, they can be distinguished by the expression of aldolase C and by the greater lipid secretory capacity in alveolar cells. Lumenal epithelial cells also vary in their expression of hormone receptor genes (Clarke 2006;Anderson and Clarke 2004;Harris et al 2004;Naylor et al 2003;Binart et al 2000). The apparent Fig.…”

Effect of Prolactin on the Population of Epithelial Cells From Ventral Prostate of Intact and Cyproterone Acetate‐Treated Peripubertal Rats: Stereological and Immunohistochemical Study

“…PL also stimulates epithelial prostatic proliferation in vitro (Nevalainen et al, 1991). Further, the local, hormone-dependent production of PL in rat prostate was demonstrated (Nevalainen et al, 1991), together with the presence of PL receptors in the epithelium from normal (Nevalainen et al, 1997;Harris et al, 2004) and pathological prostate (Leav et al, 1999).…”

Human Scalp Hair Follicles Are Both a Target and a Source of Prolactin, which Serves as an Autocrine and/or Paracrine Promoter of Apoptosis-Driven Hair Follicle Regression

“…Subsequently, this activation of the PRL-R by JAK2 turns the receptor into a receptor tyrosine kinase, which phosphorylates inactive STATs and causes them to dimerize and translocate as activated transcription factors into the nucleus, where they bind to specific DNA regions and stimulate transcription of PRL target genes. [32][33][34] In addition, the biological activity of PRL is triggered via a hormone-induced receptor homodimerization process that is regulated by tertiary features of the hormone. This feature plays an important role in the regulation of these systems by producing binding surfaces with dramatically different binding affinities to the receptor.…”

“…It is now recognized that, besides the pituitary gland, a number of extrapituitary tissues (such as placenta, uterus, mammary gland, brain, and lymphocytes) can synthesize PRL. 1,32 The PRL receptor (PRL-R) is a single-pass membranebound protein that belongs to the cytokine receptor family and transduces its signal by binding Janus kinases (JAKs) and by activating signal transducers and activators of transcription (Stat) proteins. Crosslinking of PRL-Rs by PRL brings the JAK2 that is bound to the cytoplasmic tail of each PRL-R together, leading to PRL-R phosphorylation.…”