title: Effects of tri-iodothyronine, cortisol and transcriptional inhibitors on vitamin D3-enhanced thyrotrophin secretion by rat pituitary cells in vitro.
abstract: The hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to selectively enhance agonist-induced TSH release in the rat thyrotroph in vitro. The interaction of 1,25-(OH)2D3 with tri-iodo-thyronine (T3) and cortisol was studied in primary cultures of dispersed anterior pituitary cells. TRH (1 nmol/l)-induced TSH release over 1 h was enhanced by 70% (P less than 0.01) following exposure to 10 nmol 1,25-(OH)2D3/l for 24 h. Pretreatment with T3 (1 pmol/l-1 mumol/l) for 24 h caused a dose-dependent inhibition of TRH-induced TSH release. Net TRH-induced TSH release was inhibited by 85% at T3 concentrations of 3 nmol/l or greater. Co-incubation with 1,25-(OH)2D3 resulted in enhanced TRH-induced TSH release at all T3 concentrations tested (P less than 0.001). The increment of TRH-induced TSH release resulting from 1,25-(OH)2D3 pretreatment was equivalent in the presence or absence of maximal inhibitory T3 concentrations. At 1 nmol T3/l, there was a two- to threefold relative increase in 1,25-(OH)2D3-enhanced TRH-induced TSH release. Incubation with cortisol (100 pmol/l-100 nmol/l) had no effect on basal or TRH-induced TSH release, nor did it alter 1,25-(OH)2D3-enhanced TRH-induced TSH release when added 24 h before, or at the time of addition of 1,25-(OH)2D3. Actinomycin D and alpha-amanitin abolished 1,25-(OH)2D3-enhanced TSH secretion. These data demonstrate that the action of 1,25-(OH)2D3 in the thyrotroph required new RNA transcription, and was not affected by cortisol. In the presence of T3, the response of the thyrotroph to TRH induced by 1,25-(OH)2D3 was increased. We have shown that 1,25-(OH)2D3 has significant effects on the action of TRH and T3 in vitro. These findings support the proposal that 1,25-(OH)2D3 may modulate TSH secretion in vivo.
authors.affiliation: Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Australia.
authors.forename: M C
authors.initials: MC
authors.lastname: d'Emden
authors.forename: J D
authors.initials: JD
authors.lastname: Wark
mesh_terms: D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D000546:Amanitins; D014284:Triiodothyronine; D003609:Dactinomycin; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D002117:Calcitriol; D006854:Hydrocortisone