Abstract
The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They reduce tumour size effectively and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, although the underlying mechanisms are still unknown. Thus, we investigated whether there are differences in tumour sensitivity to CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Moreover, BRC and CAB elicited cell death via different pathways; BRC induced prolactinoma cell death mainly through the apoptosis pathway, and CAB induced pituitary prolactinoma cell death mainly via the autophagic cell death pathway. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma.
Highlights
1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction Prolactinomas are the most common type of pituitary tumour and are responsible for numerous cases of hyperprolactinemia, which can lead to oligomenorrhea, amenorrhea or galactorrhea syndromes in women as well as erectile dysfunction and decreased libido in men[1,2]
These results showed that CAB can suppress the activation of the AKT/mTOR signalling pathway to induce autophagy in prolactinoma cells
In the present study, we investigated the mechanisms underlying the of difference in efficacy between BRC and CAB in patients with prolactinomas using the rat prolactinoma cell lines GH3 and MMQ
Summary
Prolactinomas are the most common type of pituitary tumour and are responsible for numerous cases of hyperprolactinemia, which can lead to oligomenorrhea, amenorrhea or galactorrhea syndromes in women as well as erectile dysfunction and decreased libido in men[1,2]. Giant prolactinomas, which are rare clinical events[3], are defined as unusually large tumours (larger than 4 cm in maximal diameter) with extremely high and obvious mass-effect symptoms, such as headache and visual field defects (VFDs)[4]. Due to their invasive clinical behaviour, giant prolactinomas are difficult to treat[4]. Mainly bromocriptine (BRC) and cabergoline (CAB), are the first-line treatment for the majority of patients with idiopathic hyperprolactinemia and prolactinomas, and they effectively suppress prolactin secretion and shrink tumour volume in most patients[6,7]. Clinical studies have shown that BRC can effectively control serum prolactin levels in 80–90% of microadenomas and 70% of large adenomas and can Official journal of the Cell Death Differentiation Association
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have