The identification of a human myometrial corticotropin-releasing hormone receptor that increases in affinity during pregnancy
| Autor: | Nathaniel G.N. Milton, Dimitris K. Grammatopoulos, H. W. P. Quartero, Edward W. Hillhouse |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Adult
endocrine system medicine.medical_specialty Time Factors Corticotropin-Releasing Hormone Endocrinology Diabetes and Metabolism Statistics as Topic Clinical Biochemistry Population Corticotropin-releasing hormone receptor Biology Binding Competitive Receptors Corticotropin-Releasing Hormone Biochemistry Corticotropin-releasing hormone Endocrinology Anterior pituitary Pregnancy Cations Internal medicine medicine Animals Humans Neurotransmitter metabolism education Receptor education.field_of_study Binding Sites Sheep Biochemistry (medical) Temperature Myometrium Hydrogen-Ion Concentration Receptors Neurotransmitter medicine.anatomical_structure Oxytocin Female hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 76:736-741 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | The concentration of immunoreactive, placentally derived CRH is increased in the peripheral circulation during the third trimester of human pregnancy. However, the function of this placental CRH is entirely unknown. A number of observations have led us to believe that CRH might influence myometrial contractility and, hence, parturition via specific receptor mechanisms. 1) In idiopathic preterm labor, plasma immunoreactive-CRH concentrations are significantly elevated compared to control values. 2) CRH and oxytocin exhibit a marked synergistic effect on myometrial contractility which is prostaglandin dependent and can be inhibited by the CRH receptor antagonist [alpha-helical CRF-(9-41)]. In view of this, we searched for specific CRH-binding sites in myometrial tissue obtained at biopsy from pregnant (cesarian section) and nonpregnant (hysterectomy) patients. To test for the presence of CRH receptors, we prepared myometrial membranes and performed binding studies using [125I]tyr-o-CRH as a ligand. The binding was found to be pH, time, temperature, and divalent cation concentration dependent and was fully reversible on addition of 1 microM unlabeled ovine CRH. In both tissues, there was a single, specific, homogenous, high affinity population of CRH receptors. Scatchard analysis of the specific binding sites revealed dissociation constants of 250-300 and 30-60 pM for the nonpregnant and pregnant myometrium, respectively. This compares with dissociation constants of 130 pM (rat anterior pituitary receptor) and 100 pM (human CRH-binding protein). This would mean that in the nonpregnant state, the equilibrium for binding is in favor of the binding protein, but during the later stages of pregnancy, the change in affinity of the receptor alters the binding in favor of the myometrial receptor. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|