ISSN:
1365-2826
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
There is increasing evidence that nitric oxide (NO) produced by NO synthase (NOS), and their signalling partners, guanylyl cyclase and cGMP, play a relevant role in growth hormone (GH) secretion from somatotrophs. We previously demonstrated that both GH-releasing hormone (GHRH; 10−8 M) and low concentrations of somatostatin (10−15 M) stimulate pig GH release in vitro, whereas a high somatostatin concentration (10−7 M) inhibits GHRH-induced GH secretion. To ascertain the possible contribution of the NOS-NO and guanylyl cyclase-cGMP routes to these responses, cultures of pituitary cells from prepubertal female pigs were treated (30 min) with GHRH (10−8 M) or somatostatin (10−7 or 10−15 M) in the absence or presence of activators or blockers of key steps of these signalling cascades, and GH release was measured. Two distinct activators of NO route, SNAP (5 × 10−4 M) or L-AME (10−3 M), similarly stimulated GH release when applied alone (with this effect being blocked by 10−7 M somatostatin), but did not alter the stimulatory effect of GHRH or 10−15 M somatostatin. Conversely, two NO pathway inhibitors, NAME (10−5 M) or haemoglobin (20 µg/ml) similarly blocked GHRH- or 10−15 M somatostatin-stimulated GH release. 8-Br-cGMP (10−8 to 10−4 M) strongly stimulated GH release, suggesting that cGMP may function as a subsequent step in the NO pathway in this system. Interestingly, 10−7 M somatostatin did not inhibit the stimulatory effect of 8-Br-cGMP. Moreover, although 8-Br-cGMP did not modify the effect of GHRH, it enhanced GH release stimulated by 10−15 M somatostatin. Accordingly, a specific guanylyl cyclase inhibitor, LY-83, 583 (10−5 M) did not alter 10−15 M somatostatin-induced GH release, whereas it blocked GHRH-induced GH secretion. These results demonstrate for the first time that the NOS/NO signalling pathway contributes critically to the stimulatory effects of both GHRH and low-concentration somatostatin on GH release, and that, conversely, the subsequent guanylyl cyclase/cGMP step only mediates GHRH- and not low-concentration somatostatin-induced GH secretion from somatotrophs.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1365-2826.2005.01345.x
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