The effect of sex steroids on pituitary luteinizing hormone releasing hormone (LHRH) receptor number and affinity was studied in adult castrated male and female rats treated for 2 weeks with 17β-estradiol (E2), testosterone (T), 5α-dihydrotestosterone (DHT) or progesterone (P) alone or in combination. The effect of chronic treatment with the potent LHRH agonist [D-Ser(TBU)6, des-Gly-NH210] LHRH ethylamide, Buserelin, was studied in intact and castrated animals. [125I]-Buserelin was used as tracer to measure LHRH receptors in individual pituitaries. Daily treatment of intact male rats for 2 weeks with Buserelin (200 ng) increased pituitary LHRH receptor concentration while the same treatment in castrated animals reversed by 60% the elevated levels found after orchidectomy. In the female rat, the elevation of pituitary LHRH receptors which follows ovariectomy is similarly reversed by chronic treatment with the LHRH agonist. Treatment with an anti-LHRH serum leads to an almost complete loss of pituitary LHRH receptors measured 24 h after injection of the antiserum. Daily treatment with E2 (1 μg) or P (4 mg) alone has no effect on pituitary LHRH receptor levels in adult castrated male or female animals, while a 35-50% receptor loss is observed after combined E2 + P treatment. Daily administration of T or DHT (500 μg) causes a 40-50% reduction of pituitary [125I]-Buserelin binding to pituitary homogenate in castrated animals of both sexes. Similar K(D) values for [125I]-Buserelin binding (0.19±0.01 nM) are obtained in all groups, thus indicating that the changes of [125I]-Buserelin binding induced by treatment with sex steroids or the LHRH agonist are due to changes in the number of LHRH binding sites and not to modifications in affinity of the LHRH receptor. Treatment for 2 weeks with T, DHT or Buserelin completely abolishes the luteinizing hormone (LH) response to 200 ng LHRh while there is a tendency for increased responsiveness after E2 treatment and no change after administration of P alone. A close correlation is found between the number of LHRH binding sites and the total surface area of gonadotrophs, thus suggesting that the changes of receptor number induced by chronic sex steroid or LHRH agonist treatment are associated with parallel changes of surface membrane area rather than to changes of the density of LHRH receptors. In addition, the present data show that the marked changes of LH responsiveness to LHRH are not always accompanied by parallel changes of pituitary LHRH receptor levels, thus suggesting that postreceptor events are also important sites for the control of gonadotropin secretion.
|Number of pages||13|
|Journal||Biology of Reproduction|
|Publication status||Published - 1982|
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology