We examined the expression of functional
growth hormone secretagogue receptors (GHS-R) in a series of 30 human
pituitary adenomas-six secreting GH, three GH-PRL, six
prolactin (PRL), five
adrenocorticotrophic hormone (
ACTH), one
thyroid stimulating hormone (TSH), four gonadotroph and five non-secreting
adenomas. By
reverse transcriptase polymerase chain reaction (RT-PCR), the coexpression of the two GHS-R
isoforms (Ia and Ib) was found in all the GH-, GH-PRL- and PRL-secreting
adenomas, and only in two out of three corticotroph, two out of four gonadotroph and one out of five non-secreting tumours. They were absent in the TSH-secreting
adenoma. The PCR products of GHS-R Ia and Ib were identical in size to those from two normal pituitaries. PCR cloning and sequencing of
isoforms performed in two
somatotroph adenomas revealed only two single, silent base mutations. Triple in-situ hybridization showed colocalization of GHS-R
mRNA with messengers of GH and PRL, conjointly or separately, in individual cells of somatotroph, mammosomatotroph, and
lactotroph adenomas. The presence of GHS-R
mRNA in cells expressing PRL
mRNA is emphasized. In cultured cells from six somatotroph and two mammosomatotroph
adenomas, the powerful GHS
MK-0677 stimulated GH release in a dose-dependent manner, with maximal effect at 6 h. Contrarily, when GHRH was applied, only three somatotrophs and two mamosomatotrophs were stimulated. In the two mammosomatotrophs, the PRL response to
MK-0677 and to GHRH was similar to the GH response. An homologous desensitization of the GHS-R and the
GHRH receptor was observed 24 h after a first stimulation by a single dose of the corresponding agonist. Heterologous desensitization was not observed. Interestingly,
MK-0677 also stimulated, in a dose-dependent way, the
hormone release of cells from all tested lactotroph and
corticotroph adenomas. The existence of a functional expression of GHS-R in somatotroph, mammosomatotroph, lactotroph and
corticotroph adenomas rises the question of the role played by GHS-R in
pituitary adenomas, particularly those not engaged in GH secretion.