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Inhibitory effect of prepro-thyrotrophin-releasing hormone (178-199) on adrenocorticotrophic hormone secretion by human corticotroph tumours
- Publication Year :
- 2010
-
Abstract
- Prepro-thyrotrophin-releasing hormone (TRH) (178-199), a 22-amino acid cleavage product of the TRH prohormone, has been postulated to act as an adrenocorticotrophin hormone (ACTH)-release inhibitor. Indeed, although in vitro evidence indicates that this peptide may inhibit basal and stimulated ACTH secretion in rodent anterior pituitary primary cultures and cell lines, not all studies concur and no study has as yet evaluated the effect of this peptide in Cushing's disease. The present study aimed to test the effect of preproTRH(178-199) in human tumoural corticotrophs. Twenty-four human ACTH-secreting pituitary tumours (13 macroadenomas, 11 microadenomas) were collected during surgery and incubated with 10 or 100 n. m preproTRH(178-199). ACTH secretion was assessed after 4 and 24 h of incubation by immunometric assay and expressed relative to levels observed in control, unchallenged wells (= 100%). Parallel experiments were performed in rat anterior pituitary primary cultures. A clear inhibition of ACTH secretion at 4 and 24 h was observed in 12 specimens (for 10 n. m ppTRH: 70 ± 4% control at 4 h and 83 ± 5% control at 24 h; for 100 n. m ppTRH: 70 ± 4% control at 4 h and 85 ± 5% control at 24 h), whereas a mild and short-lasting stimulatory effect was observed in three tumours and no changes in ACTH secretion in the remaining nine tumoural specimens. The inhibitory effect of preproTRH(178-199) was more evident in macroadenomas and significantly correlated with sensitivity to dexamethasone inhibition. Significant inhibition of ACTH secretion by preproTRH(178-199) in rat pituitary cultures was observed after 24 h of incubation. The present study conducted in a large series of human corticotroph tumours shows that preproTRH(178-199) inhibits tumoural ACTH secretion in a sizable proportion of specimens, in close relation to the size of the tumour and its sensitivity to glucocorticoid negative feedback. This appears a promising avenue of research and further studies are warranted to explore the full scope of preproTRH(178-199) as a regulator of ACTH secretion. © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd.
- Subjects :
- Male
Pituitary gland
Protein Precursor
Corticotropin-Releasing Hormone
Endocrinology, Diabetes and Metabolism
Cell Culture Techniques
Drug Evaluation, Preclinical
Dexamethasone
Cushing syndrome
Endocrinology
Peptide Fragment
Thyrotropin-Releasing Hormone
Cells, Cultured
medicine.anatomical_structure
ACTH-Secreting Pituitary Adenoma
Cushing's disease
Female
Cell Culture Technique
hormones, hormone substitutes, and hormone antagonists
Endocrine gland
Human
Adenoma
endocrine system
medicine.medical_specialty
Down-Regulation
Adrenocorticotropic hormone
Biology
Endocrine and Autonomic System
Cellular and Molecular Neuroscience
Hormone Antagonists
Thyroid-stimulating hormone
Anterior pituitary
Adrenocorticotropic Hormone
Pituitary Gland, Anterior
Internal medicine
medicine
Animals
Humans
Protein Precursors
Dose-Response Relationship, Drug
Endocrine and Autonomic Systems
Pituitary tumour
Animal
medicine.disease
Peptide Fragments
PreproTRH(178-199)
Rats
ACTH
Hormone Antagonist
Rat
Corticotropic cell
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....5d28098d85501672408de4a60d887d4b