Endocrine Abstracts (2001) 2 OC18

Pars intermedia pro-gamma-melanotropin and a cleft protease, a mitotic conspiracy in the pituitary?

PJ Lowry, K Lomthaisong, RT Gladwell & AB Bicknell

School of Animal and Microbial Sciences.

We have recently reported that a novel protease found on the surface of cells in the zona glomerulosa of the adrenal cortex specifically cleaves pro-gamma-melanotropin (pro-gamma-MSH) generating the adrenal mitogen, pro-opiomelanocortin, POMC(1-52). RT-PCR of mRNA isolated separately from the pars intermedia and pars distalis suggested that this protease is also expressed in both parts of the pituitary gland but surprisingly confocal microscopy in situ hybridisation located it to the colloid cells in the cleft. This part of the pituitary is usually ignored but this finding was corroborated by immunocytochemistry using an affinity purified antibody raised against a synthetic peptide representing the first 25 residues of the protease. Interestingly the immunoreactivity was more extensive than that found by in situ hybridisation, with finger-like projections extending into the pars distalis.

Does this finding finally give the pars intermedia and the colloid cells of the cleft a role? The poor vascularisation of the pars intermedia in mammals, its clear (POMC) biosynthetic capability but lack of significant concentrations of its products in blood would argue in favour of a paracrine role(s). Some cells of the pars distalis are known to proliferate under certain conditions e.g. lactotrophs during lactation and corticotrophs after adrenalectomy, and the question arises whether pro-gamma-MSH crosses the cleft and provides the pars distalis with the necessary mitogenic drive. Thus cells responding to chronic hypothalamic signals may also upregulate the expression of the putative mitogenic POMC(1-52) receptor which then leads to their proliferation. Indeed lactotrophs do proliferate under the influence of N-POMC peptides. Further, the C-terminal gamma-MSH fragment POMC(53-74) may be the natural ligand that activates the novel MSH receptor recently found on GH3 cells. The characterisation of the latter receptor and that for POMC(1-52) will help in substantiating this hypothesis and may throw light on the genesis of pituitary adenomas.

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