Hypogonadism in Male Patients with Pituitary Adenoma and Its Related Mechanism: A Review of Literature.

Maintaining normal gonadal axis hormone levels is important for improving the condition of male patients with pituitary adenoma. The current literature is somewhat divided on the results of evaluations of gonadal axis function in male patients with pituitary adenoma before and after treatment, and the increasing demand for better quality of life has provided motivation for this research to continue. In this article, we summarize the feasibility of using testosterone as an indicator for assessing male function and discuss the changes reported in various studies for gonadal hormones before and after treatment in male patients with pituitary adenoma. It is important for clinicians to understand the advantages of each treatment option and the effectiveness of assessing gonadal function. The rationale behind the theory that pituitary adenomas affect gonadal function and the criteria for evaluating pituitary-gonadal axis hormones should be explored in more depth.

Clinicopathological Characteristics of Plurihormonal Pituitary Adenoma.

Background: As the pathogenesis of plurihormonal pituitary adenoma (PPA) is unclear and the diagnostic criteria are inconsistent, clinicians still find it challenging to diagnose. To analyze the relationship between clinical and pathological characteristics in PPA. Methods: The clinical data of patients with 70 PPAs admitted during 2008-2010 and 2019-2020 were collected and analyzed. In particular, hormone examination using cell culture supernatant was performed to confirm PPA cases from 2019 to 2020. Results: PPA accounted for 13% of all pituitary cases recorded in the same period. There were 30 men and 40 women. Fifty-three percent of patients had one endocrine manifestation, and 1% presented with two endocrine symptoms. However, none of the patients had three endocrine manifestations. The level of one and two types of hormones was elevated in 52 (74.3%) and 5 (7.1%) patients, respectively and that of three types of hormones was increased only in one patient. Immunohistochemical staining for PRL + TSH or FSH/LH was most commonly performed (n = 17), followed by that for PRL + GH + ACTH and PRL + GH + TSH or FSH/LH (n = 14) and PRL + ACTH (n = 10). The primary culture results in vitro were consistent with the pathological findings in five (41.7%) patients. Moreover, 4 of 12 patients diagnosed with PPA during 2019-2020 tested positive for SOX2. Conclusion: The pathogenesis of PPA remains elusive due to the lack of specific clinical symptoms and endocrine changes. Examination of hormones on tumor culture supernatant is helpful for its diagnosis.

MicroRNAs in Dopamine Agonist-Resistant Prolactinoma.

Dopamine agonists (DAs) are preferred for the treatment of prolactinomas and are usually very effective. Nonetheless, 20-30% of bromocriptine- and approximately 10% of cabergoline-treated individuals exhibit resistance to DAs. In addition, the mechanism underlying this phenomenon remains elusive. In this study, we summarize the major findings regarding the role of microRNAs (miRNAs) in the pathogenesis of DA-resistant prolactinoma (DARP). Currently available evidence suggests that miRNAs are usually dysregulated in DARP and that, although controversial, the dysregulated miRNAs target the transforming growth factor (TGF)-ß, dopamine 2 receptor (D2R), or estradiol (E2)/estrogen receptor (ER) signaling pathways to mediate the therapeutic effect of DAs. These findings provide new incentives for research on innovative strategies for predicting patients' responsiveness to dopamine therapies and for developing treatment approaches. Unfortunately, recent studies tended to focus exclusively on the differential miRNA expression profiles between DARP and dopamine-sensitive prolactinoma, and no definitive consensus has been reached regarding the role of these miRNAs in the modulation mechanism. Therefore, current and future efforts should be directed toward the exploration of the mechanism underlying the dysregulation of miRNAs as well as of the target proteins that are affected by the dysregulated miRNAs. Furthermore, the modulation of the expression of dysregulated miRNAs, which target the D2R, TGF-ß, or E2/ER signaling pathways, might be a promising alternative to treat patients with DARP and improve their prognosis.

Exploiting D2 receptor ß-arrestin2-biased signalling to suppress tumour growth of pituitary adenomas.

BACKGROUND AND PURPOSE: Dopamine agonists targeting D2 receptor have been used for decades in treating pituitary adenomas. There has been little clear evidence implicating the canonical G protein signalling as the mechanism by which D2 receptor suppresses the growth of pituitary tumours. We hypothesize that ß-arrestin2-dependent signalling is the molecular mechanism dictating D2 receptor inhibitory effects on pituitary tumour growth. EXPERIMENTAL APPROACH: The involvement of G protein and ß-arrestin2 in bromocriptine-mediated growth suppression in rat MMQ and GH3 tumour cells was assessed. The anti-growth effect of a ß-arrestin2-biased agonist, UNC9994, was tested in cultured cells, tumour-bearing nude mice and primary cultured human pituitary adenomas. The effect of G protein signalling on tumour growth was also analysed by using a G protein-biased agonist, MLS1547, and a Gßγ inhibitor, gallein, in vitro. KEY RESULTS: ß-arrestin2 signalling but not G protein pathways mediated the suppressive effect of bromocriptine on pituitary tumour growth. UNC9994 inhibited pituitary tumour cell growth in vitro and in vivo. The suppressive function of UNC9994 was obtained by inducing intracellular reactive oxygen species generation through downregulating mitochondrial complex I subunit NDUFA1. The effects of Gαi/o signalling and Gßγ signalling via D2 receptor on pituitary tumour growth were cell-type-dependent. CONCLUSION AND IMPLICATIONS: Given the very low expression of Gαi/o proteins in pituitary tumours and the complexity of the responses of pituitary tumours to G protein signalling pathways, our study reveals D2 receptor ß-arrestin2-biased ligand may be a more promising choice to treat pituitary tumours with improved therapeutic selectivity.