Basal growth hormone (GH) levels are higher in female than male primates, and estradiol (E) treatment of gonadectomized primates increases serum GH. To determine if the effect of E is mediated at the level of the somatotroph, we verified the effect of E-treatment on serum GH in spayed macaques, and then examined the effect of E on GH secretion in serum-free monkey pituitary cultures. Daily blood samples were obtained from cynomolgus macaques which were spayed upon detection of menstruation and immediately implanted with either empty (n = 5) or E-filled (n = 5) 2-cm silastic capsules. The average level of GH was significantly higher (P < 0.003) in the E-treated group than in the control group (6.4 ± 0.7 vs. 3.7 ± 0.6 ng/ml). Pituitaries from rhesus monkeys were dispersed and cultured in 48-well plates on extracellular matrix in DME/F12 with insulin, transferrin, selenium. Using pituitary cells from a long-term spayed female, two plates were established with and without phenol red. Each plate was treated with E in a dose-related manner (0.001-10 nM) from days 0-18 (4 wells per dose). There was a significant dose-related increase in medium prolactin (PRL) in both plates, but E had no effect on GH. Therefore, the effect of E on GH in spayed monkeys cannot be accounted for by a direct action on somatotrophs. Additional phenol red-free pituitary cultures were established from four juvenile males, one adult male, two juvenile females, and two adult females and treated with E in a dose-related fashion for 28 days. Neither the adult male, the adult female, nor the juvenile female cultures exhibited an increase in GH with E treatment. Only the four juvenile male pituitary cultures showed a variable increase in GH with maximal responses ranging from 5 to 40% over control. This data suggested that the juvenile male pituitary contained an E-sensitive GH-secreting cell population which is not present in the other pituitary cultures. PRL and GH double-immunocytochemical staining of pituitary cultures from an adult female and a juvenile male revealed a significant population of rounded and possibly double-labeled cells in the juvenile male culture which were infrequently seen in the adult female culture. Speculatively, this population could represent mammosomato-troph stem cells that corelease GH and PRL upon stimulation.
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