Endocrine Abstracts

Background: Hyperprolactinemia, caused by chronic use of antipsychotics, is associated with impaired bone density and increased risk of fractures. We examined if calcium and vitamin D supplementation have influence on Prlr gene expression in the duodenum, vertebrae and kidneys in female rats with sulpiride-induced hyperprolactinemia.

Methods: Wistar female rats 21 weeks old were divided into: Group S: 10 rats that were intramuscular administrated Sulpiride (10 mg/kg) twice daily for 6 weeks; Group D: 10 rats that were administrated Sulpiride (10 mg/kg) twice daily for 6 weeks, calcium 50 mg daily and vitamin D 500 IU per day for last 3 weeks; and age matched nulliparous rats as a control group: 7 rats, 21 weeks old (C). Laboratory analysis included measurements of serum ionized calcium, phosphorus, urinary calcium and phosphorous excretion, osteocalcin (OC), vitamin D, and prolactin. Relative quantification of prolactin receptor (Prlr) gene expression in duodenum, vertebrae and kidneys was determined using real-time PCR.

Results: PRL concentrations were significantly higher in group S and D, compared to C (P<0.001). Ionized calcium was significantly increased in the group S compared to C (P<0.001) and without significance between group D and C. Serum phosphorus was not significantly changed in S and D compared to C. Urinary calcium was decreased in group S compared to C but without significance and significantly increased in D compared to C (P<0.001); urinary phosphorous was not significantly changed neither in S nor in D. OC was significantly decreased in group D compared to C (P<0.001) and without significance between groups S and C. Expression of the Prlr gene was significantly lower in the duodenum (P<0.01) and higher in vertebrae and kidneys in the sulpiride-induced hyperprolactinemia (S) than in the control group. Significantly higher Prlr expression in the duodenum was verified (P<0.01), along with increased Prlr gene expression in vertebrae and kidneys, in rats with sulpiride-induced hyperprolactinemia and calcium and vitamin D supplementation, than in the C group.

Conclusions: In sulpiride-induced hyperprolactinemia, down-regulation of Prlr gene expression in duodenum could be underlying reason for diminished intestinal calcium absorption. In order to maintain calcium homeostasis, since intestinal absorption is compromised, prolactin will rapidly take calcium from skeletal system, thanks to increased Prlr gene expression in the vertebra. Calcium and vitamin D supplementation in the sulpiride-induced hyperprolactinemia significantly increased Prlr gene expression in duodenum which could improve intestinal calcium absorption and reduce the harmful effect on the bone system.