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Proopiomelanocortin (POMC) is a complex precursor that comprises several peptidic hormones, including melanocyte-stimulating hormones (MSHs), adrenocorticotropic hormone (ACTH), and β-endorphin. POMC belongs to the opioid/orphanin gene family, whose precursors include either opioid (YGGF) or the orphanin/nociceptin core sequences (FGGF). This gene family diversified during early tetraploidizations of the vertebrate genome to generate four different precursors: proenkephalin (PENK), prodynorphin (PDYN), and nociceptin/proorphanin (PNOC) as well as POMC, although both PNOC and POMC seem to have arisen due to a local duplication event. POMC underwent complex evolutionary processes, including internal tandem duplications and putative coevolutionary events. Controversial and conflicting hypotheses have emerged concerning the sequenced genomes. In this article, we summarize the different evolutionary hypotheses proposed for POMC evolution.

The precise molecular mechanisms controlling progesterone receptor (PR)-mediated gene regulation within the human myometrium in pregnancy and in labour remain poorly defined. PR recruit different nuclear co-activators/co-repressors to mediate receptor-specific transcription regulation and expression of PR, and these co-factors may alter within the myometrium during pregnancy and labour. The aims of this study were to test the hypotheses that i) the human splicing and transcription factor, polypyrimidine tract binding protein-associated splicing factor (PSF), is spatially and temporally regulated in the myometrium during pregnancy and labour; ii) PSF influences the expression of myometrial PR and iii) the action of PR in regulating specific hormone response target genes in the human myometrium may involve PSF. Immunoblotting indicated that PSF expression is significantly up-regulated within the human myometrium as pregnancy progresses, in particular within the upper uterine region, and levels remain elevated in labour. Co-immunoprecipitations and DNA-binding assays show that PSF directly interacts with nuclear PR and glucocorticoid receptor (GR) and specific co-regulatory proteins, all of which have defined roles as co-activators or co-repressors in gene regulation. Over-expression and inhibition of PSF by transient transfection and RNAi respectively alters expression of myometrial PR and GR and may influence expression of two PR/GR-target genes, cyclooxygenase-2 and histone deacetylase-2. These findings are suggestive of a role for myometrial PSF as a nuclear co-regulator in the regulation of specific hormone receptor genes and their target hormone response genes.

In mammals, secretin is a 27-amino acid peptide that was first studied in 1902 by Bayliss and Starling from the extracts of the jejunal mucosa for its ability to stimulate pancreatic secretion. To date, secretin has only been identified in tetrapods, with the earliest diverged secretin found in frogs. Despite being the first hormone discovered, secretin's evolutionary origin remains enigmatic, it shows moderate sequence identity in nonmammalian tetrapods but is highly conserved in mammals. Current hypotheses suggest that although secretin has already emerged before the divergence of osteichthyans, it was lost in fish and retained only in land vertebrates. Nevertheless, the cognate receptor of secretin has been identified in both actinopterygian fish (zebrafish) and sarcopterygian fish (lungfish). However, the zebrafish secretin receptor was shown to be nonbioactive. Based on the present information that the earliest diverged bioactive secretin receptor was found in lungfish, and its ability to interact with both vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide potently suggested that secretin receptor was descended from a VPAC-like receptor gene before the Actinopterygii–Sarcopterygii split in the vertebrate lineage. Hence, secretin and secretin receptor have gone through independent evolutionary trajectories despite their concurrent emergence post-2R. A functional secretin–secretin receptor axis has probably emerged in the amphibians. Although the pleiotropic actions of secretin are well documented in the literature, only limited information of its physiological functions in nonmammalian tetrapods have been reported. To decipher the structural and functional divergence of secretin and secretin receptor, functional characterization of the ligand–receptor pair in nonmammals would be the next perspective for investigation.

Gastrin, secreted by stomach G cells in response to ingested sodium, stimulates the renal cholecystokinin B receptor (CCKBR) to increase renal sodium excretion. It is not known how dietary sodium, independent of food, can increase gastrin secretion in human G cells. However, fenofibrate (FFB), a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, increases gastrin secretion in rodents and several human gastrin-secreting cells, via a gastrin transcriptional promoter. We tested the following hypotheses: (1.) the sodium sensor in G cells plays a critical role in the sodium-mediated increase in gastrin expression/secretion, and (2.) dopamine, via the D₁R and PPAR-α, is involved. Intact human stomach antrum and G cells were compared with human gastrin-secreting gastric and ovarian adenocarcinoma cells. When extra- or intracellular sodium was increased in human antrum, human G cells, and adenocarcinoma cells, gastrin mRNA and protein expression/secretion were increased. In human G cells, the PPAR-α agonist FFB increased gastrin protein expression that was blocked by GW6471, a PPAR-α antagonist, and LE300, a D₁-like receptor antagonist. LE300 prevented the ability of FFB to increase gastrin protein expression in human G cells via the D₁R, because the D₅R, the other D₁-like receptor, is not expressed in human G cells. Human G cells also express tyrosine hydroxylase and DOPA decarboxylase, enzymes needed to synthesize dopamine. G cells in the stomach may be the sodium sensor that stimulates gastrin secretion, which enables the kidney to eliminate acutely an oral sodium load. Dopamine, via the D₁R, by interacting with PPAR-α, is involved in this process.