Truncated equine LH beta and asparagine(56)-deglycosylated equine LH alpha combine to produce a potent FSH antagonist

dc.contributor.author	Butnev, Vladimir Y.	en_US
dc.contributor.author	Singh, V.	en_US
dc.contributor.author	Nguyen, Van T.	en_US
dc.contributor.author	Bousfield, George R.	en_US
dc.date.accessioned	2012-01-24T17:48:25Z
dc.date.available	2012-01-24T17:48:25Z
dc.date.issued	2002-03	en_US
dc.identifier	11874703	en_US
dc.identifier	AG15428/ DK52383	en_US
dc.identifier	0375363	en_US
dc.identifier	JOE04323	en_US
dc.identifier.citation	The Journal of endocrinology. 2002 Mar; 172(3): 545-55.	en_US
dc.identifier.issn	0022-0795	en_US
dc.identifier.uri	http://dx.doi.org/10.1677/joe.0.1720545
dc.identifier.uri	http://hdl.handle.net/10057/4123
dc.description	Click on the DOI link below to access the article (may not be free).	en_US
dc.description.abstract	Hybrid hormone preparations were prepared by combining intact and Asn(56)-deglycosylated (N(56)dg) equine (e) LH or FSH alpha subunit preparations with truncated, des(121-149)eLH beta (eLH beta t), immunopurified, intact eLH beta or equine chorionic gonadotropin beta (eCG beta) preparations, and eFSH beta. The LH receptor-binding potencies of N(56)dg-eLH alpha:eLH beta t and N(56)dg-eFSH alpha:eLH beta t hybrids were equivalent to that of eLH; however, both N(56)dg-alpha preparations were only 3-4% as active as eLH in the rat testis Leydig cell bioassay. In the granulosa cell FSH bioassay, eLH alpha:eLH beta t stimulated progesterone synthesis and induced aromatase activity, while N(56)dg-eLH alpha:eLH beta t was completely inactive at doses up to 5 microg. N(56)dg-eLH alpha:eLH beta t inhibited progesterone production and aromatase induction elicited by 0.3 ng eFSH or 2 ng human (h) FSH. The inhibitory activities of N(56)dg-eLH alpha:eLH beta and N(56)dg-eCG alpha:eLH beta t were only 10% that of N(56)dg-eLH alpha:eLH beta t. N(56)dg-eLH alpha:eCG beta did not inhibit progesterone synthesis stimulated by eFSH at all and appeared to further stimulate aromatase induction at the highest dose tested. Preincubation of N(56)dg-eLH alpha:eLH beta and N(56)dg-eLH alpha:eLH beta t for 72 h at 37 C resulted in no loss of FSH receptor-binding activity. Preincubation resulted in 50% loss of receptor-binding activity by the eFSH preparation due to subunit dissociation, while 88% of N(56)dg-eLH alpha:eFSH beta activity was lost following 72 h, 37 C preincubation. While alpha Asn(56) oligosaccharide had no effect on eLH beta hybrid stability, it did contribute to the stability of the eFSH heterodimer.	en_US
dc.description.sponsorship	NIA NIH HHS/ NIDDK NIH HHS	en_US
dc.language.iso	eng	en_US
dc.publisher	BioScientifica Ltd.	en_US
dc.relation.ispartofseries	The Journal of endocrinology	en_US
dc.source	NLM	en_US
dc.subject	Research Support, U.S. Gov't, Non-P.H.S.	en_US
dc.subject	Research Support, U.S. Gov't, P.H.S.	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Dimerization	en_US
dc.subject.mesh	Dose-Response Relationship, Drug	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Follicle Stimulating Hormone/antagonists & inhibitors	en_US
dc.subject.mesh	Glycoprotein Hormones, alpha Subunit/metabolism	en_US
dc.subject.mesh	Granulosa Cells/drug effects	en_US
dc.subject.mesh	Horses	en_US
dc.subject.mesh	Luteinizing Hormone/chemistry	en_US
dc.subject.mesh	Radioligand Assay/methods	en_US
dc.subject.mesh	Rats	en_US
dc.subject.mesh	Recombinant Proteins/metabolism	en_US
dc.subject.mesh	Glycoprotein Hormones, alpha Subunit/metabolism	en_US
dc.subject.mesh	Granulosa Cells/metabolism	en_US
dc.subject.mesh	Luteinizing Hormone/metabolism*	en_US
dc.title	Truncated equine LH beta and asparagine(56)-deglycosylated equine LH alpha combine to produce a potent FSH antagonist	en_US
dc.type	Article	en_US
dc.description.version	peer reviewed	en_US
dc.rights.holder	Copyright @ 2002 Society for Endocrinology	en_US