The Prolactin Gene: A Paradigm of Tissue‐Specific Gene Regulation with Complex Temporal Transcription Dynamics

Abstract

Transcription of numerous mammalian genes is highly pulsatile, with bursts of expression occurring with variable duration and frequency. The presence of this stochastic or ‘noisy’ expression pattern has been relatively unexplored in tissue systems. The prolactin gene provides a model of tissue‐specific gene regulation resulting in pulsatile transcription dynamics in both cell lines and endocrine tissues. In most cell culture models, prolactin transcription appears to be highly variable between cells, with differences in transcription pulse duration and frequency. This apparently stochastic transcription is constrained by a transcriptional refractory period, which may be related to cycles of chromatin remodelling. We propose that prolactin transcription dynamics result from the summation of oscillatory cellular inputs and by regulation through chromatin remodelling cycles. Observations of transcription dynamics in cells within pituitary tissue show reduced transcriptional heterogeneity and can be grouped into a small number of distinct patterns. Thus, it appears that the tissue environment is able to reduce transcriptional noise to enable coordinated tissue responses to environmental change. We review the current knowledge on the complex tissue‐specific regulation of the prolactin gene in pituitary and extra‐pituitary sites, highlighting differences between humans and rodent experimental animal models. Within this context, we describe the transcription dynamics of prolactin gene expression and how this may relate to specific processes occurring within the cell.

Plasticity of the Prolactin (PRL) Axis: Mechanisms Underlying Regulation of Output in Female Mice

“…Gene Expression A range of factors have been described which affect PRL gene expression in rats (reviewed in [64]), but it is the regulation by DA and estrogen, which is the most clearly defined in rodents. The Pou1f1 transcription factor, required for adult PRL gene expression, mediates both the positive and negative regulation of PRL gene transcription by estrogen [65] and hypothalamic DA [66], respectively.…”

Prolactin gene polymorphism (− 1149 G/T) is associated with hyperprolactinemia in patients with schizophrenia treated with antipsychotics

“…In humans, the PRL locus consists of a single gene that contains five coding exons, which is controlled by a pituitaryspecific promoter, and a non-coding exon, which is controlled by an alternative promoter. The latter promoter drives expression in non-pituitary tissues (Featherstone et al, 2012). Thus, apart from its role as a pituitary hormone, prolactin is also produced as a cytokine by immune cells; its receptor belongs to the family of cytokine receptors type 1 (Peeva et al, 2003).…”

Localization and expression patterns of prolactin-like protein J in mouse testis

“…The prolactin (PRL) family is comprised of multiple proteins that regulate a plethora of biological functions (1)(2)(3)(4)(5)(6). In rats and mice, the PRL gene family consists of at least 20 well-characterized genes, including placental lactogens, PRL-like proteins (PLPs), PRL-related proteins, proliferin and proliferin-related protein (7).…”

“…In rats and mice, the PRL gene family consists of at least 20 well-characterized genes, including placental lactogens, PRL-like proteins (PLPs), PRL-related proteins, proliferin and proliferin-related protein (7). The PRL family genes, located on chromosome 13 in mice and chromosome 17 in rats, are mainly expressed in the pituitary gland, uterus and placenta (1)(2)(3)(4)(5)(6). These proteins demonstrate a unique spatio-temporal expression profile and strongly influence various aspects of gestation (1,(7)(8)(9).…”