In the last few years, molecular studies on pituitary adenomas have yi
elded evidence supporting a primary pituitary origin of these tumors.
Although the existence of genomic alterations in tumoral cells is stro
ngly suggested by the fact that almost all pituitary adenomas are mono
clonal in origin, structural genetic abnormalities such as rearrangeme
nt, deletion or mutation, which could result in transcriptional activa
tion, have been identified in a minority of tumors. As far as the poss
ible loss of anti-oncogenes in pituitary tumors is concerned, gene alt
erations have not been found in the p53 nor in the retinoblastoma gene
, while loss of chromosome 11q13 sequences, which contain the deduced
location of the yet uncloned MEN-1 gene, has been reported in a subset
of GH-secreting adenomas. With regard to the activation of dominant o
ncogenes in the process of tumor formation, activating mutations of ei
ther the Gs alpha-subunit or the ras gene have been identified in a la
rge proportion of GH-secreting adenomas and in individual particularly
invasive tumours, respectively. Promoting agents such as hypothalamic
neurohormones and growth factors may be required for the selective gr
owth of genetically altered cells. In this respect, it is worth noting
that receptor/postreceptor alterations occurring in pituitary tumors
may cause an increased action of stimulatory neurohormones with growth
promoting properties as well as defective action of inhibitory inputs
.