Isolation and characterization of the human prolactin gene.

Abstract

Prolactin (PRL) and growth hormone (GH) genes derive from a common ancestor and still share some sequence homologies. Their expression in the pituitary gland is regulated in opposite directions by most of the many hormones acting on them. This provides an interesting system to study sequences involved in gene expression. Using a human PRL cDNA clone as a probe, we screened a human genomic DNA library in lambda phage and isolated a single recombinant comprising the whole hPRL gene. It was characterized by restriction endonuclease mapping and cDNA hybridization, by DNA heteroduplex analysis and by nucleotide sequencing. The hPRL gene is present as a single copy per haploid genome, is approximately 10 kb long and contains four introns, three of which interrupt the coding sequence at the same locations as in the known GH and PRL genes. The origin of transcription was determined by S1 mapping on prolactinoma mRNAs. The search for direct and inverted repeats, as well as dyad symmetries was carried out in the 900‐bp sequenced in the 5′‐flanking region. Sequence homologies between hPRL, hGH and rPRL were derived from computer drawn matrices for these upstream regions.

Expression of prolactin mRNA and of prolactin-like proteins in endothelial cells: evidence for autocrine effects

“…The 384-bp transcript was found to be devoid of a 108-bp region comprising codons encoding for amino acids 41-76. This region corresponds to exon 3 in the human PRL gene and in the rat PRL gene (Gubbins et al 1980, Truong et al 1984. Although genomic sequence data for bovine PRL remain incomplete, the homology found among species strongly suggests that this small transcript could correspond to a novel PRL mRNA in which exon 2 is being spliced directly onto exon 4 without affecting the reading frame.…”

“…The 492-bp product has the sequence of the cloned bPRL cDNA, in which exon 2 is followed by exon 3 (Truong et al 1984). In the 384-bp product, exon 2 is followed by exon 4, denoting the loss of exon 3 of bPRL cDNA.…”

EGF stimulates Pit-1 independent transcription of the human prolactin pituitary promoter in human breast cancer SK-BR-3 cells through its proximal AP-1 response element

“…In pituitary, the hPRL mRNA starts with exon 1b at the pituitary start site and transcription is controlled by the pituitary promoter, extending to possibly 5.8 kb of upstream region (Truong et al, 1984). The pituitary promoter contains many binding sites for the pituitary-specific transcription factor Pit-1 and several binding sites for ubiquitous transcription factors (Van de Weerdt et al, 2000), the most prominent being the estrogen receptor.…”

Expression of the human growth hormone variant gene in cultured fibroblasts and transgenic mice.

“…Any two of the five genes in the family are at least 92% homologous, suggesting a relatively recent series ofgene duplications (2,3). The hGH gene family members are also related to the prolactin gene (10), with hGH and prolactin sharing =35% amino acid homology.…”