Carcinoma of the prostate with Cushing's syndrome

A case is described of a patient with a smallcell prostatic carcinoma containing immunoreactive CRH, in conjunction with ACTH-dependent Cushing's syndrome. The serum concentrations of CRH, ACTH, β-endorphin and calcitonin were all found to be above normal. Post-mortem examination revealed a prostatic tumour with multiple metastases, and a diffuse hyperplasia of pituitary corticotropic cells and adrenal cortical cells. In sections of the primary prostatic tumour, immunoreactive cells were demonstrable with antisera raised against human CRH, TSH, calcitonin and somatostatin, but not with antisera against ACTH or β-endorphin. By radioimmunoassay the CRH-like material could also be demonstrated in extract of the prostatic tumour and the material from both plasma and tumour extract eluted at the position of human CRH on gel chromatography (Sephadex G-75). These findings provide support for the interpretation that the patient's Cushing's syndrome was due to a CRH-producing prostatic tumour. Finally, the origin and the clinical significance of the neuroendocrine cells in the prostatic carcinoma is discussed.

Chromatographic characteristics of pro-opiomelanocortin-derived peptides from the rat transplantable tumour 7315a

ABSTRACT Adrenocorticotrophin (ACTH) and other proopiomelanocortin (POMC)-derived peptides produced by the 7315a corticomammotrophic tumour have been poorly studied although they elicit profound hypertrophy and hyperplasia in the adrenal glands of recipient Buffalo rats. Tumour extracts were chromatographed on Sephadex G-75 and fractions monitored for POMC-derived peptides by four radioimmunoassay (RIA) systems: ACTH, α-MSH, β-lipotrophin (β-LPH)/endorphin and N-terminal POMC (N-POMC). Chromatograms were compared with those of pars distalis extracts from normal Buffalo rats. All four RIA systems detected immunoreactive material in tumour extracts. ACTH, β-LPH/ endorphin and N-POMC were present in approximately equimolar amounts (ACTH content 93·40 ± 5·27 (s.e.m.) pmol/g) whereas α-MSH was present in smaller amounts (2·83± 0·13 pmol/g). Total peptide content correlated well with tumour weight. ACTH immunoreactivity (IR) in Sephadex chromatograms was located in a large 20 000 mol. wt peak, an ACTH(1–39) peak and a smaller peak coinciding with ACTH(1–24). The latter two peaks showed biological activity consistent with ACTH(1–39) and an ACTH (1–24)-like peptide respectively. The β-LPH/endorphin RIA revealed a peak eluting at approximately 20 000 mol. wt which could not be ascribed to any known POMC peptide containing the endorphin sequence. A β-LPH-like peak, a β-endorphin-like peak and a smaller-sized peak, which contained the bulk of the β-LPH/endorphin IR, were detected; the low molecular weight peak probably representing α- or γ-endorphin. The N-POMC RIA revealed a 20 000 mol. wt peak and a wide peak which could not be completely resolved into two peaks, and which probably represented N-POMC(1–95) and (N-POMC(1–74). No 30 000 mol. wt precursor could be detected with any of the RIA systems employed. Sephadex chromatography of material released from perfused dispersed tumour cells revealed identical IR peaks with all RIA systems used. Glycosylation of tumour POMC peptides was assessed by Concanavalin A–agarose (Con A) chromatography of pooled IR peaks from Sephadex chromatograms. The 20 000 mol. wt (both IR-ACTH and IR-N-POMC) peak, IR-N-POMC(1–95) and IR-N-POMC(1–74) peaks all bound to Con A and were specifically eluted with methylglucoside. Sephadex G-75 and Con A chromatography of pooled pars distalis extracts from normal Buffalo rats were performed. They showed significant differences, compared with tumour extract chromatograms, with all the RIA systems employed. It is concluded that the 7315a tumour processes POMC in a different manner when compared with normal Buffalo rat pars distalis and that it may be used as an interesting model in which to study the processing of POMC. In addition it may shed light on the role of POMC-derived peptides, other than ACTH(1–39), on adrenal growth and function. J. Endocr. (1987) 112, 417–425

STUDIES ON ECTOPIC ACTH-PRODUCING TUMOURS.

ABSTRACT In order to elucidate whether ectopic ACTH-producing tumours elaborate corticotrophin-releasing factors (CRF)-like materials, the CRF-like activity of tumour extracts was measured by the in vitro pituitary incubation method. Seven out of 12 tumour extracts with suspected ACTH-producing tumours showed CRF-like activity. No correlation was found between ACTH and CRF-like activities in tumour extracts in which both activities were present. The dose-response curve of a tumour extract was almost parallel to that of crude CRF (NIAMDD) and clearly different from those of lysine-8-vasopressin and arginine-vasopressin, both of which showed CRF-like activity by this assay method. Trypsin digestion considerably lowered the CRF-like activity of a tumour extract. These results suggest that ectopic production of CRF-like substance(s) occurs more frequently than was supposed previously, especially in ACTH-producing tumours.