Neuronal nitric oxide synthase gene expression in human pituitary tumours: a possible association with somatotroph adenomas and growth hormone-releasing hormone gene expression.
OBJECTIVE
Nitric oxide (NO) has been implicated in the control of the secretory response to growth hormone-releasing hormone (GHRH) and may also modify GH release in response to excitatory aminoacids. Although rat and mouse pituitary cell lines have been shown to express neuronal NO synthase (nNOS), there has until now been no information on nNOS gene expression in human pituitary adenomas. Our objective was to provide such data and correlate the presence of nNOS transcripts with GHRH transcripts.


METHODS
Pituitary adenoma tissue was obtained from a random selection of 32 patients with somatotrophadenomas, 16 patients with corticotroph adenomas, 39 patients with endocrinologically inactive adenomas and nine patients with macroprolactinomas undergoing transsphenoidal hypophysectomy.


METHODS
Transcripts for nNOS and GHRH were identified in frozen tissue sections by in situ hybridization histochemistry using synthetic 35S-labelled oligodeoxynucleotide probes with 100% homology to the target transcript.


RESULTS
Neuronal NOS transcripts were identified in one of 16 corticotroph adenomas (6%), one of nine macroprolactinomas (11%), six of 39 endocrinologically inactive adenomas (15%) and 13 of 32 somatotroph adenomas (41%). GHRH transcripts were found in a similar distribution to nNOS transcripts in 10 of the 13 nNOS-expressing somatotroph adenomas, and in three of the four remaining adenomas from which suitable tissue was available. Cross-hybridization of the nNOS and GHRH probes to the same target was excluded by including rat brain sections cut through the arcuate nucleus as hybridization controls. Furthermore, two different nNOS oligodeoxynucleotide probes complementary to different regions of the target transcript produced identical results.


CONCLUSIONS
These results suggest that there is a close correlation between nNOS gene expression and 'ectopic' expression of GHRH in human pituitary tumours, especially somatotroph adenomas. The relevance of these findings from a functional or pathologenic viewpoint remains unclear, but the data again emphasize that it is not just GH secretion that distinguishes somatotroph adenomas from other pituitary tumours.
Ueta
Y
Y
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. yoichi@med.uoeh-u.ac.jp
Levy
A
A
Powell
M P
MP
Lightman
S L
SL
Kinoshita
Y
Y
Yokota
A
A
Shibuya
I
I
Yamashita
H
H
D000236:Adenoma / Q000201:enzymology* / Q000378:metabolism; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001345:Autoradiography; D005260:Female; D015870:Gene Expression; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000032:analysis / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D010911:Pituitary Neoplasms / Q000201:enzymology* / Q000378:metabolism; D015175:Prolactinoma / Q000201:enzymology; D051381:Rats
D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat