Stimulation of gonadal cells by lutropins such as human chorionic gonadotropin (hCG) is often transient and followed by down-regulation and/or desensitization of lutropin receptors (LHR). Here we describe desensitization/resensitization of LHR in Y-1 adrenal cell lines (termed Y-1L) expressing a rat cDNA lacking most 5' and 3' LHR untranslated regions under the control of a metallothionein promoter. Using a simple morphological assay in which stimulated cells are round and unstimulated cells are flat, we identified clones that rounded and remained round and others that became insensitive to lutropin stimulation and reverted to their flat appearance within 2-4 h. Flattened cells were insensitive to further hormonal stimulation but rounded after treatments with cholera toxin, forskolin, or cyclic AMP, showing that loss of responsiveness was associated with an early step in signal transduction, not loss of rounding potential. Removing the lutropin stimulus for at least 90-120 min reversed hormone insensitivity, even in the presence of the protein synthesis inhibitor puromycin. The number of surface bound receptors did not change during a cycle of rounding/flattening and hCG bound to rounded or flattened cells was replaced equally by radioiodinated hCG during incubations at 4 degrees C. Thus, desensitization/resensitization of LHR in Y-1L cells occurred in the absence of new receptor synthesis, receptor degradation, or receptor recycling. These observations suggest that LHR desensitization/resensitization in Y-1L cells was closely coupled to receptor occupancy and that this cell line may be useful for identifying factors that modulate the activities of occupied receptors.

This article has been cited by other articles:

				K A Slot, M de Boer-Brouwer, M Houweling, A B Vaandrager, J H Dorrington, and K J Teerds Luteinizing hormone inhibits Fas-induced apoptosis in ovarian surface epithelial cell lines J. Endocrinol., February 1, 2006; 188(2): 227 - 239. [Abstract] [Full Text] [PDF]

				N. A. Rahman, S. Kiiveri, A. Rivero-Muller, J. Levallet, S. Vierre, J. Kero, D. B. Wilson, M. Heikinheimo, and I. Huhtaniemi Adrenocortical Tumorigenesis in Transgenic Mice Expressing the Inhibin {alpha}-Subunit Promoter/Simian Virus 40 T-Antigen Transgene: Relationship between Ectopic Expression of Luteinizing Hormone Receptor and Transcription Factor GATA-4 Mol. Endocrinol., October 1, 2004; 18(10): 2553 - 2569. [Abstract] [Full Text] [PDF]

				R. H. Massol, J. E. Larsen, Y. Fujinaga, W. I. Lencer, and T. Kirchhausen Cholera Toxin Toxicity Does Not Require Functional Arf6- and Dynamin-dependent Endocytic Pathways Mol. Biol. Cell, August 1, 2004; 15(8): 3631 - 3641. [Abstract] [Full Text] [PDF]

				R. D. Horvat, B. G. Barisas, and D. A. Roess Luteinizing Hormone Receptors Are Self-Associated in Slowly Diffusing Complexes during Receptor Desensitization Mol. Endocrinol., April 1, 2001; 15(4): 534 - 542. [Abstract] [Full Text]