Andrea Ramos de Castro Moreira, Ericka Trarbach, Cristina Bellotti Formiga Bueno, Anna Louise Stellfeld Monteiro, Isabella Pacetti Pajaro Grande, Mario Padula, Gustavo Arantes Rosa Maciel, Andrea Glezer
The Journal of clinical endocrinology and metabolism 2023 Jun 16Knockout prolactin receptor gene (PRL-R) mice are animal models for prolactinomas and PRL acts via autocrine/paracrine inhibiting lactotroph proliferation. Recently, variants of the PRL-R were identified in prolactinoma patients and their frequency was higher compared to individuals from the genomic database. We analyzed PRL-R variants frequency in an extensive cohort of prolactinoma patients and evaluated their association with clinical, laboratorial, and imaging characteristics and hormonal response to cabergoline. Observational, retrospective, and cross-sectional study. This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center. Study participants included adults with sporadic prolactinomas treated with cabergoline, where response to therapy was defined by prolactin normalization with up to 3 mg/week doses. DNA was extracted from blood samples and the PRL-R was analyzed by polymerase chain reaction techniques and automatic sequencing. The association of PRL-R variants with serum prolactin levels, maximal tumor diameter, tumor parasellar invasiveness, and response to cabergoline was analyzed. We found 6 PRL-R variants: p.Ile100(76)Val, p.Ile170(146)Leu, p.Glu400(376)Gln/p.Asn516(492)Ile, p.Glu470Asp e p.Ala591Pro; the last 2 are newly described in prolactinomas' patients. The variants p.Glu400(376)Gln/p.Asn516(492)Ile and p.Ala591Pro were more frequent amongst patients compared to genomic databases, and the p.Asn516(492)Ile showed pathogenic potential using in silico analysis as previously described. PRL-R variants were associated with male sex (P = 0.015), higher serum PRL levels (P = 0.007), larger tumors (P = 0.001), and cabergoline resistance (P < 0.001). The prolactin/prolactin receptor system seems to be related to prolactinoma tumorigenesis and cabergoline resistance. Additional studies are needed to better understand the PRL-R variants' role and their potential as therapeutic targets. © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Andrea Ramos de Castro Moreira, Ericka Trarbach, Cristina Bellotti Formiga Bueno, Anna Louise Stellfeld Monteiro, Isabella Pacetti Pajaro Grande, Mario Padula, Gustavo Arantes Rosa Maciel, Andrea Glezer. PRL-R Variants Are Not Only Associated With Prolactinomas But Also With Dopamine Agonist Resistance. The Journal of clinical endocrinology and metabolism. 2023 Jun 16;108(7):e450-e457
PMID: 36638053
View Full Text