Mid-aged and aged wild-type and progestin receptor knockout (PRKO) mice demonstrate rapid progesterone and 3α,5α-THP-facilitated lordosis
| Autor: | Kanako Sumida, Cheryl A. Frye, B. W. O’Malley, D. W. Pfaff, John P. Lydon |
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| Rok vydání: | 2006 |
| Předmět: |
Aging
medicine.medical_specialty Neuroactive steroid Lordosis medicine.drug_class Injections Subcutaneous Posture Radioimmunoassay Biology Mice Sexual Behavior Animal chemistry.chemical_compound Receptors GABA Internal medicine medicine Animals Desoxycorticosterone Receptor GABA Agonists Progesterone Mice Knockout Pharmacology Estradiol Muscimol GABAA receptor Allopregnanolone medicine.disease Endocrinology chemistry Injections Intravenous Knockout mouse Female Receptors Progesterone Progestin |
| Zdroj: | Psychopharmacology. 185:423-432 |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s00213-005-0300-4 |
| Popis: | Progesterone (P) and its 5alpha-reduced metabolite, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP), facilitate sexual behavior of rodents via agonist-like actions at intracellular progestin receptors (PRs) and membrane GABA(A)/benzodiazepine receptor complexes (GBRs), respectively.Given that ovarian secretion of progestins declines with aging, whether or not senescent mice are responsive to progestins was of interest.Homozygous PR knockout (PRKO) or wild-type mice that were between 10-12 (mid-aged) or 20-24 (aged) months of age were administered P or 3alpha,5alpha-THP, and the effect on lordosis were examined. Effects of a progestin-priming regimen that enhances PR-mediated (experiment 1) or more rapid, PR-independent effects of progestins (experiments 2 and 3) on sexual behavior were examined. Levels of P, 3alpha,5alpha-THP, and muscimol binding were examined in tissues from aged mice (experiment 4).Wild-type, but not PRKO, mice were responsive when primed with 17beta-estradiol (E(2); 0.5 microg) and administered P (500 microg, subcutaneously). Mid-aged wild-type mice demonstrated greater increases in lordosis 6 h later compared to their pre-P, baseline test than did aged wild-type mice (experiment 1). Lordosis of younger and older wild-type, but not PRKO, mice was significantly increased within 5 min of intravenous (IV) administration of P (100 ng), compared with E(2)-priming alone (experiment 2). However, wild-type and PRKO mice demonstrated significant increases in lordosis 5 min after IV administration of 3alpha,5alpha-THP, an effect which was more pronounced in mid-aged than in aged animals (100 ng-experiment 3). In tissues from aged wild-type and PRKO mice, levels of P, 3alpha,5alpha-THP, and muscimol binding were increased by P administration (experiment 4). PR binding was lower in the cortex of PRKO than that of wild-type mice.Mid-aged and aged PRKO and wild-type mice demonstrated rapid P or 3alpha,5alpha-THP-facilitated lordosis that may be, in part, independent of activity at PRs. |
| Databáze: | OpenAIRE |
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