The Mutant Growth Hormone-Releasing Hormone (GHRH) Receptor of the Little Mouse Does Not Bind GHRH1.
نویسندگان
چکیده
The little mouse is a dwarf strain characterized by low levels of GH, pituitary hypoplasia, and an unresponsiveness to treatment with exogenous GHRH. The defect has been mapped to a missense mutation in the GHRH receptor gene that abolishes the function of the receptor, but the mechanism of this inactivation is unknown. Receptor function might be affected at the level of protein expression, maturation and processing, localization to the cell surface, ligand binding, or signaling. In this study, Western blots, using antiserum raised against the GHRH receptor and immunoprecipitation analysis of epitope-tagged receptors, demonstrate that both wild-type and mutant receptor proteins are expressed at equivalent levels in transfected cells. Immunofluorescence analysis of intact and permeabilized cells expressing the epitope-tagged receptors suggests that wild-type and little mouse receptors are similarly localized to the cell surface. A species homologous binding assay was developed and used to show that 125I-mouse GHRH binds with high affinity to the wild-type mouse receptor but not to the little mutant receptor. Consistent with this, the mutant receptor fails to stimulate intracellular cAMP accumulation. Our results demonstrate that the little mutation does not dramatically affect the expression level, glycosylation, or cellular localization of the receptor protein but that it blocks specific GHRH binding, and therefore, signaling does not take place.
منابع مشابه
بررسی چند شکلی ژنتیکی و فراوانی آللی جایگاه ژنی GHRH (Growth-hormone-releasing hormone) در گاوهای سرابی ایران
انتخاب حیوان بر اساس نشانگرهای مولکولی یکی از جدیدترین روشهای اصلاحی است که می‌تواند باعث بهبود صحت پیش‌بینی و پاسخ به انتخاب شود. GHRH (Growth-hormone-releasing hormone) یکیازژنهایبرگزیدهبرایاستراتژی‌هایانتخاببراساسمارکرمی‌باشد.براساسگزارشاتموجود، چندشکلی‌هایژن بهطورمعنی‌داریباصفاتاجزایشیروتولیدآنارتباطدارد. به منظور بررسی چندشکلی (پلی‌مورفیسم) مکان ژنی GHRH در نژاد سرابی، از 112 رأس گاو ...
متن کاملPituitary hypoplasia in patients with a mutation in the growth hormone-releasing hormone receptor gene.
BACKGROUND AND PURPOSE Several anatomic abnormalities of the pituitary gland have been described as occurring in association with congenital growth hormone deficiency, including hypoplasia of the adenohypophysis, truncation of the pituitary stalk, and ectopia of the neurohypophysis. Their pathogenesis, however, is obscure. Normal pituitary development is dependent on the sequential expression o...
متن کاملComparison of Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variant 1 in Different Stages of Endometriosis
متن کامل
Inhibition of mutant p53 expression and growth of DMS-153 small cell lung carcinoma by antagonists of growth hormone-releasing hormone and bombesin.
We investigated the effects of growth hormone-releasing hormone (GHRH) antagonists, JV-1-65 and JV-1-63, and bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC-3940-II on DMS-153 human small cell lung carcinoma xenografted into nude mice. Treatment with 10 microg/day JV-1-65 or RC-3940-II decreased tumor volume by 28% (P < 0.05) and 77% (P < 0.01), respectively, after 42 days compared wi...
متن کاملIdentification of binding domains of the growth hormone-releasing hormone receptor by analysis of mutant and chimeric receptor proteins.
The hypothalamic peptide GH-releasing hormone (GHRH) stimulates the release of GH from the pituitary through binding and activation of the GHRH receptor, which belongs to the family of G protein-coupled receptors. The objective of this study was to identify regions of the receptor critical for interaction with the ligand by expressing and analyzing truncated and chimeric epitope-tagged GHRH rec...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Endocrinology
دوره 140 11 شماره
صفحات -
تاریخ انتشار 1999