Gene and protein expression in pituitary corticotroph
adenomas: a systematic review of the literature.
The lateral part of the pars distalis: pars distalis (PaD), acidophilic cell (AC), basophilic cell (BC), chromophobe cell (CC), sinusoid (Sin), somatotroph cell (SC), thyrotroph cell (TC), gonadotroph cell (GC), corticotroph
A separate analysis showed that when corticotroph
pituitary tumor cells were treated with levoketoconazole and racemic ketoconazole, only levoketoconazole demonstrated inhibition of ACTH secretion after just three days of treatment, whereas both levoketoconazole and racemic ketoconazole inhibited ACTH secretion after seven days of treatment.
Diagnosis of a corticotroph
adenoma was confirmed later in 1 patient at autopsy.
ACTH, the product of proopiomelanocortin gene (Pomc), is secreted from the corticotroph
cells of the anterior pituitary.
The same attempt made by the corticotroph
cells to overcome cortisol deficiency is (unsuccessfully) performed by the gonadotroph cells, which produce high amounts of luteinizing (LH) and follicle-stimulating (FSH) hormone in response to undetectable sex hormone levels.
Roughly 15% of all pituitary adenomas are corticotroph
adenomas arising from TPIT-lineage adenohypophyseal cells (TPIT = T-box protein 19) with a peak incidence in patients of 30-50 years .
(1,8) Three main pathways appear relevant: a prolactin-GH-thyroidstimulating hormone (TSH) pathway regulated by transcription factor Pit-1, (9-11) a gonadotroph pathway regulated by steroidogenic factor 1 (SF-1), (12,13) and a corticotroph
pathway mediated by T-box transcription factor (Tpit).
This idea is supported by the evidence that (1) under excess and prolonged HPA axis activation, the expression of the inhibitory SOCS protein induced by gp130 cytokine (via JAK/STAT pathway) activation can, in turn, inhibit further corticotroph
(via JAK/STAT) signaling and that (2) the application of IL-6 in nanomolar concentration range in adrenal chromaffin cells  (comparable to those observed during sepsis ) can activate ERK 1/2 and STAT3 pathways and lead to increased expression of target genes such as secreted neuropeptides including galanin, PTHrP, G-protein-coupled receptor (GPR), stanniocalcin-1 (STC1) and hypoxia-inducible factor 1[alpha] (HIF-1[alpha]) (Figure 2).
After being stimulated, neurons of the paraventricular nucleus of the hypothalamus release corticotropin-releasing hormone (CRH), which will be transported by hypothalamic-pituitary portal circulation and stimulate pituitary corticotroph
cells to cleave proopiomelanocortin (POMC) in adrenocorticotrophic hormone (ACTH) .
According to their study, short-term hypothyroidism was associated with increased pituitary corticotroph
responsiveness to corticotropin-releasing hormone in contrast with long-term hypothyroidism (36).
Background: Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph
adenomas provide exciting advances in this field.