Changes in the regulation of calcium metabolism and bone calcium content during growth in the absence of endogenous prolactin and during hyperprolactinemia: A longitudinal study in male and female Wistar rats

Abstract

Since endogenous prolactin has been shown to enhance food consumption, calcium absorption, and bone calcium turnover in the pregnant rat, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in 3-day balance studies of female Wistar rats from the age of 3 to 11 weeks. The study was divided into two parts. In part I, calcium metabolism in males and females was compared. In part II, 3-week old female rats were divided into 5 groups: (i) control animals receiving 0.9% NaCl; (ii) animals receiving 6 mg bromocriptine/kg/day (- PRLendo group); (iii) animals receiving 2.5 mg ovine prolactin/kg/day (+PRLexo); (iv) sham-operated animals receiving 0.9% NaCl, and (v) animals with two extra pituitaries implanted under the renal capsule, receiving 0.9% NaCl (AP group). Results showed that rapid growth occurred between 3 and 6 weeks with maximum fractional calcium absorption and calcium retention at 5 weeks of age in both sexes. The data also showed a physiological significance of endogenous prolactin in enhancing calcium absorption and retention in 5 week old rats. In an absence of prolactin, peak calcium absorption was delayed in 7-week old animals, and vertebral calcium content of 11-week old animals was reduced by 18%. Hyperprolactinemia in the AP group was found to enhance fractional calcium absorption and calcium retention at 7, 9, and 11 weeks and increased the femoral calcium content by 16%. It could be concluded that a physiological role of prolactin is the stimulation of calcium absorption and maintainance of bone calcium content during growth and development.

Femoral bone mineral density and bone mineral content in bromocriptine-treated pregnant and lactating rats

“…Interestingly, in contrast to non-mated rats in which PRL predominantly affected trabecular sites [3,4], PRL induced net bone gain in both trabecular and cortical parts of femur of L8 and L14 rats, presumably to expand the calcium storage pool. Therefore, the present findings, together with the facts that PRL is able to stimulate intestinal calcium absorption and renal calcium reabsorption [1,15,23], suggested that PRL orchestrated total body calcium metabolism during lactation to guarantee an adequate calcium supply for milk production.…”

“…Herein, by using ex vivo densitometric measurement, BMD and BMC of pregnant rats were found to increase at both femoral metaphysis and diaphysis. Despite the lack of evidence for the underlying mechanism, we speculated that the enhanced intestinal calcium absorption, in part, due to elevated serum PRL, placental lactogen and/or 1,25(OH) 2 D 3 levels, was responsible for supplying calcium both for fetuses, and for maternal trabecular and cortical bone calcium accretion [15,22,23], thereby leading to increases in ash weight, calcium content, and cross-sectional area of femur [1,24]. Changes in the size and crosssectional area of femur without proportional change in the total calcium content partially explained why BMC changes occurred in an absence of BMD change.…”

“…PRL surge during suckling (*400-650 ng/mL) may further contribute to the elevated BMC, since short-term hyperprolactinemia of 2-4 weeks could increase bone calcium content in the rat femur, and further augment calcium absorption in the small intestine [1,15,26]. Besides metaphysis, PRL also had a positive effect on the femoral diaphysis of L8 and L14 rats, despite having no effect on the cortical sites in non-mated rats [4].…”

“…In some experiments, prior to the removal of femora, pregnant and lactating rats were administered for 7 days with 4 mg/kg per day bromocriptine s.c., which have been known to diminish plasma PRL in pregnant and lactating rats [1,9]. Thus, each group consisted of vehicle-treated mated (pregnant or lactating) rats, bromocriptine-treated mated rats, and vehicle-treated age-matched non-mated control rats.…”

“…Previous investigations in non-mated female rats demonstrated that short-term exposure to high plasma prolactin (PRL) levels induced by 4 weeks of anterior pituitary transplantation (AP) led to net bone gain, while prolonged PRL exposure longer than 4 weeks gradually led to net bone loss [1,2]. Such hyperprolactinemic effects appeared to be observed primarily at the trabecular sites, e.g., vertebrae and sternum, but not the cortical sites, e.g., tibiae and femora [3,4].…”