Abstract
In the thyroid, thyrotropin (TSH) stimulates both growth and function, and stimulates the production of cAMP which reproduces most of the effects of TSH. Here, we report evidence that TSH stimulates the mitogen-activated protein (MAP) kinase cascade through a cAMP-independent pathway, in human thyroid. TSH stimulated MAP kinase activity (4-9-fold the basal level) measured in the cytosolic fractions of primary cultured thyroid follicles. Maximal activity was reached after 20 min and remained sustained for 1-3 h, TSH being as potent as EGF; EC50 was 1.5 nM TSH. Only a single isoform of MAP kinase (p42) was detected in the follicles. p42 was phosphorylated on tyrosine residues and showed a reduced electrophoretic mobility in follicles stimulated by TSH. All these effects on MAP kinase were decreased by preincubation of the follicles with human anti-TSH receptor antibodies. The stimulation of MAP kinase by TSH was neither blocked by pertussis toxin nor reproduced by forskolin, cholera toxin, or 8-bromo-cAMP. In conclusion, in human thyroid cells, in contrast with previous observations on dog thyroid cells, TSH stimulates strongly MAP kinase through a pertussis toxin-insensitive and cAMP-independent pathway.
Highlights
In the thyroid, thyrotropin (TSH) stimulates both growth and function, and stimulates the production of cAMP which reproduces most of the effects of TSH
In human thyroid cells, in contrast with previous observations on dog thyroid cells, TSH stimulates strongly mitogen-activated protein (MAP) kinase through a pertussis toxin-insensitive and cAMP-independent pathway
TSH induces cell proliferation but does not stimulate MAP kinase. This cell proliferation is most probably mediated by an elevation in intracellular cAMP, since TSH stimulates adenylyl cyclase in these cells, and forskolin is able to fully reproduce the TSH effect on cell division [13]
Summary
3693-3697, 1995 Printed in U.S.A. Stimulation of Mitogen-activated Protein Kinase by Thyrotropin in Primary Cultured Human Thyroid Follicles*. We report evidence that TSH stimulates the mitogen-activated protein (MAP) kinase cascade through a cAMP-independent pathway, in human thyroid. Mitogen-activated protein kinase (MAP1 kinase or Erk) is an essential component of a signaling cascade, rapidly activated by MAP kinaselErk kinase, which phosphorylates it on both a threonine and a tyrosine residue [1, 2] This cascade can be stimulated in various cell types [3] by a range of growth factors, and by hormones acting through receptors that are coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) [4,5,6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
