PRL-R Variants Are Not Only Associated With Prolactinomas But Also With Dopamine Agonist Resistance.
J Clin Endocrinol Metab
; 108(7): e450-e457, 2023 06 16.
Article
en En
| MEDLINE
| ID: mdl-36638053
ABSTRACT
CONTEXT Knockout 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. OBJECTIVE:
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.DESIGN:
Observational, retrospective, and cross-sectional study.SETTING:
This study took place at the Neuroendocrinology Unit of Clinics Hospital, Medical School of University of São Paulo, Brazil, a tertiary referral center. PATIENTS ANDMETHODS:
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.RESULTS:
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).CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Hipofisarias
/
Prolactinoma
Tipo de estudio:
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
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Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2023
Tipo del documento:
Article
País de afiliación:
Brasil