Time-courses of the appearance/disappearance of nuclear androgen + receptor complexes in the brain and adenohypophysis following testosterone administration/withdrawal to castrated male rats: relationships with gonadotropin secretion.
We characterized the temporal dynamics of brain and pituitary cell nuclear androgen receptor binding and serum androgen and gonadotropin levels associated with the implantation and removal of testosterone (T)-filled Silastic capsules into performed s.c. flank pouches of castrated, awake male rats. These capsules produced serum T levels in the physiologic range. The number of cell nuclear androgen + receptor complexes, as measured in an exchange assay using [3H]R1881, increased 15-fold at 0.5 h after capsule insertion in the HPAS (combined hypothalamus, preoptic area, amygdala and septum) and anterior pituitary gland, but then showed a second progressive rise within the next 8 h. This pattern suggests that T exerts an initial action in the tissues to alter the affinity and/or number of available androgen receptors. There was a lag time of 2-4 h to the first indication of negative feedback suppression of LH secretion. Serum LH levels declined only slightly at 4 h after capsule insertion but continued to fall thereafter, reaching undetectable values by 24 h. In contrast, serum FSH levels declined only slightly after 24 h of T exposure. After removal of the T capsules, serum T levels declined to castrate values within 2 h at which time the level of androgen + receptor complexes had fallen to 60% in the brain and pituitary. Serum LH and FSH concentrations were unchanged at 2 h after capsule removal, but rose significantly within the next 2 h. The data indicate that the occupation of androgen receptors rapidly changes in response to variations in circulating T in a fashion that implicates their involvement in the expression of this steroid's negative feedback actions on gonadotropin secretion.
Krey
L C
LC
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.
McGinnis
M Y
MY
D000728:Androgens / Q000032:analysis*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002467:Cell Nucleus / Q000032:analysis; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D010903:Pituitary Gland, Anterior / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D000728:Androgens; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone