RESUMO
A mucoepidermoid carcinoma of the lung (ICD classification 8430/3) resected from a patient with no clinical signs of pituitary-adrenal alterations was transplanted into 2-month-old athymic nu/nu nude mice, with the purpose of studying the effects exerted by the human tumour on the host hypothalamo-pituitary-adrenal axis. The tumour produces peptides derived from different regions of pro-opiomelanocortin (POMC: ACTH, 7.6 +/- 0.7; N-terminal POMC, 6.6 +/- 0.6; beta-LPH/endorphin, 7.3 +/- 0.7; and alpha-MSH;3.8 +/- 0.5 pmol/g wet tissue) and the neuropeptides corticotrophin-releasing hormone and arginine vasopressin (CRH: 3.6 +/- 0.4 and AVP: 1.1 +/- 0.2 pmol/g wet tissue). Immunohistochemical staining of consecutive sections of the tumour indicated that staining of tumour cells for the different peptides was not uniform and although some cells co-stained with CRH and AVP, POMC-positive cells appeared to be distinct from CRH and AVP cells. Tumour extracts were chromatographed on Sephadex G-75 and fractions monitored for POMC-derived peptides. A single peak with characteristics of alpha-MSH was detected. The ACTH, N-POMC and beta-LPH/endorphin radioimmunoassays (RIA) detected a peak at large molecular weight, eluting at the position expected for POMC. These RIA systems also revealed an ACTH(1-39) peak and another peak which probably correspond to 13 kDa ACTH, a peak eluting at the position of hN-POMC(1-48), a beta-LPH-like peak, and a smaller sized peak which may represent alpha- or gamma-endorphin. The ACTH, N-POMC and beta-LPH/endorphin contents of anterior lobe (AL) extracts, but not neutrointermediate lobe (NIL) extracts, showed a striking decrease in tumour-bearing (TB) nude mice. However, while no difference was seen in the alpha-MSH content of AL extract between TB and control (C) nude mice, it decreased in NIL extracts of TB animals. The contents of CRH and AVP in stalk-median eminence extracts of TB nude mice was significantly lower than that of C nude mice. Basal plasma corticosteroids were raised in TB nude mice at levels comparable to those in stressed C nude mice, and although adrenal weights did not vary between TB and C nude mice, morphological changes indicating hypertrophy were found in the adrenal glands of the host animals. It was concluded that the tumour dramatically alters the hypothalamo-pituitary-adrenal axis of the host, and that it may be a useful model for studying tumour-host interactions in ectopic hormone-producing tumours.
Assuntos
Arginina Vasopressina/biossíntese , Hormônio Liberador da Corticotropina/biossíntese , Neoplasias Pulmonares/metabolismo , Pró-Opiomelanocortina/biossíntese , Hormônio Adrenocorticotrópico/análise , Animais , Carcinoma/metabolismo , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Hormônios Estimuladores de Melanócitos/análise , Camundongos , Camundongos Nus , Transplante de Neoplasias , Adeno-Hipófise/análise , Sistema Hipófise-Suprarrenal/fisiopatologiaRESUMO
When histological sections of noninnervated kidney grafts of pituitary pars intermedia were immunohistochemically processed for the demonstration of either alpha melanocyte-stimulating hormone or adrenocorticotropic hormone, chromophilic (dark) and chromophobic (light) cells could be detected. The latter, which were not detected in the intact intermedia, were interpreted as hyperactive cells, since they lacked secretory granules and displayed an increased nuclear area. The administration of ergocryptine prevented the development of light cells. Moreover, after chronic stress (swimming), some cells appeared less intensely granulated than dark cells. The results suggest that the pars intermedia is composed of parenchymal cells with different sensitivities to dopamine. Light cells would be subject to a greater dopamine-induced inhibitory influence than dark cells. The appearance of partially degranulated cells after stress points to a participation of the grafts in this event and indicates that innervation of the intermedia is not an indispensable condition for its contribution to stress.
Assuntos
Dopamina/fisiologia , Hipófise/transplante , Hormônio Adrenocorticotrópico/análise , Animais , Feminino , Imuno-Histoquímica , Hormônios Estimuladores de Melanócitos/análise , Hipófise/citologia , Hipófise/fisiologia , Ratos , Ratos Endogâmicos , Estresse Fisiológico/fisiopatologiaRESUMO
1. An in vitro bioassay for melanotropic peptide utilizing reflectance measurements of toad skin (Bufo ictericus ictericus) is described as an alternative to the commonly used Rana pipiens bioassay. 2. The toad skin bioassay is as sensitive to melanotropins and melanin concentrating hormone (MCH) as the frog bioassay. 3. On the basis of parallel dose-response curves obtained with the toad skin assay we found that beta-MSH is slightly less active than alpha-MSH, whereas the synthetic analogue [Nle4-D-Phe7]-alpha-MSH is about 10 times more potent and exhibits prolonged biological activity. 4. MCH, a putative neurohormone, can also be bioassayed in the in vitro toad skin bioassay, since it has alpha-MSH-like activity on amphibian melanocytes. 5. Since neither adreno- nor cholinoceptors are present in the toad melanocytes, the assay provides great specificity and sensitivity for the determination of melanotropin activity in tissue or blood.