Articles 
Carroll, R.S., Corrigan, A.Z., Vale, W., and Chin, 
W.W. 1991. Activin stabilizes follicle-stimulating 
hormone-/? messenger ribonucleic acid levels. En- 
docrinology 129:1721-1726. 
Carroll, R.S., Kowash, P.M., Lofgren, J.A., Schwall, 
R.H., and Chin W.W. \ 99\. In vivo regulation of 
FSH synthesis by inhibin and activin. Endocrinol- 
ogy 129:3299-3304. 
Childs, G.V., Taub, K., Jones, K.E., and Chin, 
W.W. 1991. Triiodothyronine receptor ^-2 
messenger ribonucleic acid expression by 
somatotropes and thyrotropes: effect of propyl - 
thiouracil-induced hypothyroidism in rats. Endo- 
crinology 129:2767-2773. 
Kaiser, U.B., Lee, B.L., Carroll, R.S., Unabia, G., 
Chin, W.W., and Childs, G.V. 1992. FoUistatin 
gene expression in the pituitary: localization in 
gonadotropes and folliculostellate cells in dies- 
trous rats. Endocrinology 130:3048-3056. 
Spanjaard, R.A., Darling, D.S., and Chin, W.W. 
1991 . Ligand-binding and heterodimerization ac- 
tivities of a conserved region in the ligand-bind- 
ing domain of the thyroid hormone receptor. 
Proc Natl Acad Sci USA 88:8587-859 1 . 
Sunday, M.E., Choi, N., Spindel, E.R., Chin, W.W., 
and Mark, E. 1991- Gastrin-releasing peptide 
gene expression in small cell and large cell undif- 
ferentiated lung carcinomas. Hum Pathol 22: 
1030-1039. 
Yen, P.M., Darling, D.S., Carter, R.L., Forgione, M., 
Umeda, P.K., and Chin, W.W. 1992. Triiodothy- 
ronine (T3) decreases binding to DNA by T3- 
receptor homodimers but not receptor-auxiliary 
protein heterodimers. / Biol Chem 267:3565- 
3568. 
Yen, P.M., Darling, D.S., and Chin, W.W. 1991. 
Basal and thyroid hormone receptor auxiliary pro- 
tein-enhanced binding of thyroid hormone recep- 
tor isoforms to native thyroid hormone response 
elements. Endocrinology 129:3331-3336. 
Yen, P.M., Sunday, M.E., Darling, D.S., and Chin, 
W.W. 1992. Isoform-specific thyroid hormone 
receptor antibodies detect multiple thyroid hor- 
mone receptors in rat and human pituitaries. En- 
docrinology 130:1539-1546. 
Zhao, D., Yang, J., Jones, K.E., Gerald, C, Suzuki, 
Y., Hogan, P.G., Chin, W.W., and Tashjian, A.H., 
Jr. 1992. Molecular cloning of a complementary 
deoxyribonucleic acid encoding the thyrotropin- 
releasing hormone receptor and regulation of its 
messenger ribonucleic acid in rat GH cells. Endo- 
crinology 130:3529-3536. 
TRANSCRIPTIONAL REGULATION OF CELLULAR DIFFERENTIATION 
Gerald R. Crabtree, M.D., Associate Investigator 
Tracing a Signal Transmission Pathway 
from Cell Membrane to Nucleus 
The immune response begins when antigen is pre- 
sented to a T cell eliciting a characteristic series of 
cellular changes referred to as T cell activation. In- 
cluded among these changes are the production of 
cytokines that control cell fate decisions and differ- 
entiation and proliferation among precursors of B 
cells, granulocytes, and macrophages. The produc- 
tion of these cytokines by activated T cells is largely 
responsible for coordinating the actions of cells in- 
volved in the immune response, and their lack prob- 
ably explains the severe effects of removing T cell 
function, as in AIDS (acquired immune deficiency 
syndrome) or with drugs such as cyclosporin A. Ef- 
forts in Dr. Crabtree's laboratory have led to an un- 
derstanding of several of the steps involved in trans- 
mitting signals from the antigen receptor to the 
early activation genes responsible for the coordina- 
tion of the immune response. 
The Calcium-activated Phosphatase 
Calcineurin Relays Signals 
from the Cell Membrane to the Nucleus 
The drugs cyclosporin A and FK-506 block the 
transfer of signals from the cell membrane of T cells 
to the nucleus by acting at a previously unknown 
step. Past studies done in the Crabtree laboratory, as 
well as those of Drs. Walter Neubert in Germany and 
Mike Hall in Switzerland, led to the formulation of 
the hypothesis that these drugs produce their effects 
by forming an inhibitory complex with their bind- 
ing protein cyclophilin. This led to the search for 
CELL BIOLOGY AND REGULATION 37 
