Minireview: Extrapituitary prolactin: an update on the distribution, regulation, and functions

Abstract

Prolactin (PRL) is an important hormone with many diverse functions. Although it is predominantly produced by lactrotrophs of the pituitary there are a number of other organs, cells, and tissues in which PRL is expressed and secreted. The impact of this extrapituitary PRL (ePRL) on localized metabolism and cellular functions is gaining widespread attention. In 1996, a comprehensive review on ePRL was published. However, since this time, there have been a number of advancements in ePRL research. This includes a greater understanding of the components of the control elements located within the superdistal promoter of the ePRL gene. Furthermore, several new sites of ePRL have been discovered, each under unique control by a range of transcription factors and elements. The functional role of ePRL at each of the expression sites also varies widely leading to gender and site bias. This review aims to provide an update to the research conducted on ePRL since the 1996 review. The focus is on new data concerning the sites of ePRL expression, its regulation, and its function within the organs in which it is expressed.

Figure 1.

Control elements within the superdistal promoter of the dPRL gene. The entire promoter length is more than 2 kb (panel a) and contains 2 enhancer regions. One of the regions (panel b) ranges from −148 bp to −395 from the transcriptional start site and contains several activator (bottom, various colors) and repressor (top, in red) binding sites (adapted from Lynch et al (33)). A second enhancer region (panel c) ranges from −1505 to −2040. GR, glucocorticoid receptor; HNF-3, hepatocyte nuclear factor 3; NF-Y, nuclear factor Y; USF, upstream stimulatory factor.

Figure 2.

Activation and control of hair follicle PRL. Two mechanisms exist depending on the animal. For seasonal control (circled) timer cells stimulate PRL-secretory cells that effect the growth phases of the hair follicle. A second mechanism is dependent of the phase of the hair growth cycle. PRL and its receptor are expressed in hair matrix keratinocytes during different phases of the hair growth cycle. PRL inhibits hair-shaft elongation and hair-bulb keratinocyte proliferation. Additionally, it stimulates premature catagen development and increased hair-bulb keratinocyte apoptosis through autocrine/paracrine activity.

Figure 3.

The profile of PRL release from incubated visceral (Vis) and sc human adipose explants, as determined by the Nb2 bioassay. Left panel, obese women (BMI 48 ± 2; n= 22); middle panel, obese men (BMI 50 ± 1; n = 13); right panel, nonobese men and women (BMI 26 ± 1; n = 15). Note the dissimilar secretory profile of PRL by the 2 fat depots, the effects of obesity, and the progressive rise in PRL, suggesting removal from an inhibitory control (modified from Hugo et al (91)). BMI, body mass index.

Figure 4.

Schematics of the major organs/tissues that express PRL. The pituitary gland serves as the largest source of circulating PRL, which affects all organs that express the PRL-R. The major organs/tissues that express ePRL and were covered in this review are shown in blue.