A Pituitary Cell Type Coexpressing Messenger Ribonucleic Acid of Proopiomelanocortin and the Glycoprotein Hormone α-Subunit in Neonatal Rat and Chicken: Rapid Decline with Age and Reappearancein Vitrounder Regulatory Pressure of Corticotropin-Releasing Hormone in the Rat

Abstract

Promiscuous hormone mRNA expression in the pituitary remains poorly understood. We examined by means of RT-PCR and immunostaining whether glycoprotein hormone alpha-subunit (alphaGSU) could be coexpressed with proopiomelanocortin (POMC) in vivo and under pressure of CRH in vitro. Cells coexpressing alphaGSU and POMC mRNA amounted to 2.6% of the cells in ex vivo rat pituitary at birth [postnatal d 1 (P1)], fell to much lower level at P14, and were undetectable in adulthood. In cultured pituitary aggregates of P14 rats, alphaGSU/POMC cells remained scarce but represented up to 6.6% after chronic treatment with CRH but not leukemia inhibitory factor. CRH was less effective in aggregates from P1 and adult rats. The total alphaGSU population ex vivo at P1 was two times smaller than at P14, but in culture it expanded 2.5 times, concomitantly with a reciprocal change in POMC cell abundance. Tpit transcripts were detected in POMC-only and alphaGSU/POMC cells but not in alphaGSU-only cells. Cells coexpressing alphaGSU and POMC mRNA were relatively abundant in P14 chicken pituitary and aggregate cultures, but occurrence was not affected by CRH. Immunostaining showed alphaGSU and POMC colocalization in sporadic cells in intact rat pituitary and CRH-treated cultures at P1 but not at P14 and adult age. The data demonstrate the occurrence of cells coexpressing alphaGSU and POMC in rat and chicken pituitary. The developmental dynamics of this cell population and its response to CRH in vitro in the rat suggest a relationship of these cells with the embryonic branching of the POMC and alphaGSU cell lineages and their mutually opposite developmental course during early postnatal life.

Stem Cells, Differentiation and Cell Cycle Control in Pituitary

“…For example, our analysis of Tpit-positive cells during pituitary development led us to identify a very small number of cells (5-20 cells per pituitary) that appeared positive for both Tpit and SF1, and we have shown transcriptional antagonism between these two factors such that the activity of one will ultimately predominate over the other [8]. These observations are consistent with the existence of rare cells positive for POMC and αGSU [17]. Since it appears that cell fate decisions may be established in progenitors after their exit from the cell cycle, the relationship between progenitor cycle exit and differentiation may thus be critical to set these processes in motion.…”

Stem Cells in the Postnatal Pituitary?

“…As a notable side remark, it is well documented that during certain (patho-)physiological conditions, defined bi- or plurihormonal cells arise of which the function is as yet uncertain, such as cells with GH and gonadotropins before ovulation [6, 18], with ACTH and gonadotropins during the stress non-responsive period [68], with GH and PRL during pregnancy [13, 58], with TSH and ACTH during cold stress [56], with TSH and GH during hypothyroidism [12, 16], and with two or more hormone mRNAs in a combination phenotypical for developmental stage [69, 70] and for trophic stimulus [70,71,72,73]. Often raised hypotheses are that these cells represent either intermediate cells, or multipotential reserve or progenitor cells that differentiate into the desired cell type depending on the hormonal claim of the organism [9].…”

“…For instance, GH + cells are frequently detected just beneath the marginal epithelium in the normal male rat, but disappear after castration to be replaced by some LH + cells [129], suggesting that marginal cells give rise to these endocrine cells. We recently detected double αGSU + POMC + cells in the proximity of the cleft, bihormonal cells hypothesized to represent precursor cells [70]. Obviously, an alternative explanation for all these observations is that marginal cells are supportive or regulatory for the differentiation process, rather than being direct predecessors.…”

Endogenous Cannabinoids: Structure and Metabolism

“…We also showed that N-glycosylation is essential for bioactivity and that certain glycosylated isoforms stimulate PRL mRNA level whereas others have a mitogenic action in lactotrophs (160). That a subpopulation of gonadotrophs is capable of synthesising N-POMC was shown at the mRNA level by means of single cell reverse transcription-polymerase chain reaction (RT-PCR) (161, 162), and some cells also show immunoreactive N-POMC and αGSU colocalisation (161). Nonglycosylated N-POMC, prepared by recombinant synthesis, keeps a specific mitogenic action on lactotrophs (and no other cell types) but its efficacy is weaker and, importantly, the effect is mediated via the γ3-melanocyte-stimulating hormone (MSH) moiety in its C-terminal domain by the melanocortin-3 receptor, whereas glycosylated N-POMC has no action through the melanocortin-3 receptor (163).…”

“…This phenomenon may pave the way to explore whether urocortins influence the release of αGSU in mammals as well, particularly because cells exist in rat as well as chicken pituitary that express both POMC and αGSU (161). …”