Somatostatin inhibition of growth hormone secretion by somatotropes from male, female, and androgen receptor-deficient rats: evidence for differing sensitivities.
To investigate the role of somatostatin (SRIF) in regulating sexually dimorphic GH secretion, we used a reverse hemolytic plaque assay and acutely dispersed somatotropes from age-matched normal male, normal female, and androgen receptor-deficient, testicular feminized (Tfm) rats. Hemolytic plaques were developed after a 90-min incubation in the presence of GH antiserum, 10 nM GH-releasing hormone (GHRH), and the following concentrations of SRIF: 0, 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 nM. Additional studies were performed with 0 or 100 nM SRIF in the absence of GHRH. The absolute number of somatotropes (x10(6); mean +/- SEM) recovered from the pituitaries of Tfm rats (1.73 +/- 0.18) was significantly greater than that from the males (1.11 +/- 0.13; P = 0.01); the number from female rats (1.30 +/- 0.15) was not different from that of either male or Tfm animals. GHRH-stimulated GH secretion, as estimated by the mean GH plaque area (micron2 x 10(4); mean +/- SEM) in the absence of SRIF, was greater for somatotropes from male rats (3.36 +/- 0.41) than that for either Tfm (2.27 +/- 0.32; P = 0.02) or female (1.78 +/- 0.24; P = 0.001) rats; values for the latter two groups did not differ. However, mean GH plaque areas for each group during maximal SRIF inhibition in either the presence or absence of GHRH were indistinguishable from each other and from mean plaque areas obtained under basal conditions. As demonstrated by a lesser EC50 value (0.04 +/- 0.02 nM; mean +/- SEM), somatotropes from female rats were more sensitive to the inhibitory effect of SRIF than were those from either male (EC50 = 1.82 +/- 0.45; P = 0.0001) or Tfm (EC50 = 0.74 +/- 0.22, P = 0.0001) rats; values for the latter two groups were indistinguishable. These observed differences suggest that gender and/or the gonadal hormone environment may be important determinants of the inhibitory effects of SRIF on GH secretion by the somatotrope. While these gender-associated differences may represent effects of the gonadal hormones directly on the somatotrope, they could reflect modulation of the secretion of hypothalamic SRIF and/or GHRH by the prevailing gonadal hormone environment. Such gender-related differences may contribute to the overall sex-dependent patterns of GH secretion in the intact animal.
Kerrigan
J R
JR
Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908.
Martha
P M
PM
Krieg
R J
RJ
Rogol
A D
AD
Evans
W S
WS
D013734:Androgen-Insensitivity Syndrome / Q000503:physiopathology; D000818:Animals; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011944:Receptors, Androgen / Q000172:deficiency*; D012727:Sex Characteristics; D013004:Somatostatin / Q000494:pharmacology*
D011944:Receptors, Androgen; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone