O-249 Calcium directly influences pituitary function through the Calcium Sensing Receptor (CaSR)

Abstract

Abstract Study question Does calcium have a direct effect on pituitary function through CaSR? Summary answer CaSR is important for Hypothalamus-pituitary-gonadal (HPG) axis signaling, and lack of CaSR in the anterior pituitary leads to smaller reproductive organs in female mice. What is known already In a randomized clinical trial, prepubertal children were given calcium supplementation or placebo and girls in the intervention group went into puberty 5 months earlier than the placebo group. This effect was not detected in the boys who participated. CaSR is the main receptor for systemic calcium homeostasis, and its presence has been established in the anterior pituitary. Study design, size, duration We performed a mouse study comparing knock-out mice with a deletion of the CaSR in the anterior pituitary to wildtype mice. 13/13 female and 6/13 male knock-out/controls mice were included in the study. Participants/materials, setting, methods Female and male knock-out and control mice were sacrificed at 8 weeks. We obtained blood samples and reproductive organs was dissected, weighted and stored at -80 °C or stored in formalin before being paraffin embedded. Main results and the role of chance Female reproductive organs showed significantly lower weight when comparing CaSR knock-out to control mice. This includes ovary weight (3.7 mg vs. 6.4 mg; p = 0.0004) and uterus weight (27.9 mg vs. 67.0 mg; p = 0.0008). The weight difference was still significant after correcting for total body weight (organ weight/total body weight%): (0.02176 vs. 0,03534; p = 0.0035 and 0.1788 vs. 0.3826; p = 0.0023 respectively). We did not observe a significant difference in male reproductive organs, nor any difference in pituitary weight in either sex. Limitations, reasons for caution The difference in reproductive organ weights is interesting, but it is also an early finding. Further analysis of the collected organs and blood samples will be conducted to further investigate the phenotype of the mouse model. We are also looking into correcting weight differences for estrous cycle effects. Wider implications of the findings If CaSR proves to be important for the regulation of the HPG-axis, it has a clinical perspective since CaSR can be modulated by the drug Cinacalcet, an allosteric agonist of CaSR, already on the market where it is used to treat kidney patients. Trial registration number Not applicable