7B2, a new protein secreted by human functionless pituitary tumours, in vitro

Abstract

Abstract. A novel pituitary protein, 7B2, of approximately 180 amino acids has been suggested to colocalise with LH in the pituitary gonadotropes. Increased secretion of LH is known to occur in functionless pituitary tumours. We have therefore measured 7B2 immunoreactive equivalents in the 24-h medium of explant pituitary cultures prepared from 17 functionless, 20 somatotropic, 16 PRL secreting and 8 corticotropic adenomas. A synthetic fragment corresponding to amino acids 23–39 of 7B2 was used to raise antisera (rabbits), prepare radiolabel (chloramine T iodination) and also serve as the assay standard. 7B2-immunoreactive equivalents in the medium from the functionless tumours was 517 ± 149 pmol/l, significantly higher than that of the somatotropic tumours (248 ± 90 pmol/l, P < 0.05), prolactinomas (108 ± 37 pmol/l, P < 0.001) and corticotropin producing adenomas (107 ± 77 pmol/l, P < 0.001) (one-way analysis of variance). Gel permeation chromatography of medium obtained from functionless tumours revealed two immunoreactive 7B2 peaks one eluting at a coefficient of 0.28 corresponding to that of normal human pituitary extract and another eluting at a coefficient of 0.59. Gel chromatography profiles of medium obtained from somatotropic tumours contained similar immunoreactive 7B2 peaks (elution coefficient 0.28 and 0.57). These findings demonstrate that 7B2-like material is secreted by pituitary adenomas in explant culture with the highest level from functionless tumour cultures.

Pituitary protein 7B2 plasma levels in patients with liver disease: Comparisons with other hormones and neuropeptides

“…The 7B2-null mice with Cushing’s disease may be saved early in life by an adrenalectomy (55). Neither our plasma ACTH tumours of Cushing’s patients (26,56), nor those studied by Natori et al (57,58) allow the conclusion that 7B2-IR levels in plasma are increased in Cushing’s patients, and corticotrophic adenomas have not shown increased 7B2 secretion in vitro , although 7B2 is concomitantly secreted with ACTH by AtT-20 tumourous cells in vitro (56). It has been suggested that the lethal phenotype that is exhibited by 7B2-null mice with a complex Cushing’s disease-like pathology, is due to intermediate lobe ACTH hypersecretion as a consequence of the interruption of PC2-mediated peptide processing, as well as undefined consequences of the loss of 7B2.…”

“…7B2 cDNA cloning from various species has demonstrated the high evolutionary conservation of the 7B2 molecule, suggesting that 7B2 may be biologically relevant. In particular, the overall residue identity is extremely high (90–96%) among mammals, relatively high (67–83%) between mammals and frogs or fish, and low (17–22%) between vertebrates and invertebrates (26,27). Initially, 7B2 was revealed to be located in the pituitary gonadotrophs (26,27) and to respond to exogenous LH-releasing hormone (LHRH) (26).…”

“…In particular, the overall residue identity is extremely high (90–96%) among mammals, relatively high (67–83%) between mammals and frogs or fish, and low (17–22%) between vertebrates and invertebrates (26,27). Initially, 7B2 was revealed to be located in the pituitary gonadotrophs (26,27) and to respond to exogenous LH-releasing hormone (LHRH) (26). 7B2 has also been demonstrated to be located in tissues that are primary neuronal (the brain and adrenal medulla) or endocrine (pituitary, thyroid and pancreas) tissues, or those that are known to carry a sub-population of neuroendocrine cells (gastrointestinal tract).…”

“…The highest levels are detected in the anterior lobe of the pituitary, followed by the neurointer-mediate lobe, hypothalamus, adrenal medulla, thyroid gland and pancreas (27). In cell cultures (normal pituitary cells), the secretion of 7B2 appears to be unaffected by GHRH and CRH, but is increased by LHRH (26,27). …”

Expression of the neuroendocrine cell marker 7B2 in human ACTH secreting tumours

“…7B2 had not been found in normal or tumoral corticotroph cells (Deng et al, 1986;Suzuki et al, 1986;Venetikou et al, 1988;Steel et a[., 1988) until our recent results in the mouse tumour cell line AtT-20 (Vieau et al 1991b). These results had suggested that 7B2 had the potential to be a specific marker of non-pituitary ACTH secreting tumours in man.…”