Gender differences in the response of CD-1 mouse bone to parathyroid hormone: potential role of IGF-I

Abstract

Parathyroid hormone (PTH) exerts both catabolic and anabolic actions on bone. Studies on the skeletal effects of PTH have seldom considered the effects of gender. Our study was designed to determine whether the response of mouse bone to PTH differed according to sex. As a first step, we analyzed gender differences with respect to bone mass and structural properties of 4 month old PTH treated (80 microg/kg per day for 2 weeks) male and female CD-1 mice. PTH significantly increased fat free weight/body weight, periosteal bone formation rate, mineral apposition rate, and endosteal single labeling surface, while significantly decreasing medullary area in male mice compared with vehicle treated controls, but induced no significant changes in female mice. We then analyzed the gender differences in bone marrow stromal cells (BMSC) isolated from 4 month old male and female CD-1 mice following treatment with PTH (80 microg/kg per day for 2 weeks). PTH significantly increased the osteogenic colony number and the alkaline phosphatase (ALP) activity (ALP/cell) by day 14 in cultures of BMSCs from male and female mice. PTH also increased the mRNA level of receptor activator of nuclear factor kappaB ligand in the bone tissue (marrow removed) of both females and males. However, PTH increased the mRNA levels of IGF-I and IGF-IR only in the bones of male mice. Our results indicate that on balance a 2-weeks course of PTH is anabolic on cortical bone in this mouse strain. These effects are more evident in the male mouse. These differences between male and female mice may reflect the greater response to PTH of IGF-I and IGF-IR gene expression in males enhancing the anabolic effect on cortical bone.

Figure 1

Gender differences in the response of FFW/BW of tibia to PTH. Results are expressed as mean ±s.d. There were nine females and seven males in the vehicle group, and eight females and six males in the PTH-treated group. a, P<0·05 female control vs male control; b, P<0·05 control vs PTH treatment.

Figure 2

Gender differences in periosteal and endosteal bone formation at the tibiofibular junction as assessed by bone histomorphometry. Results are expressed as mean ±s.d. (A) Periosteal bone formation rate (BFR/BS). (B) Mineral apposition rate (MAR). (C) Endosteal single labeling surface (sLS/BS). (D) Medullary area. (E) Cortical bone area. There are nine females, five males in the vehicle group, and six females, five males in the PTH-treated group. a, P<0·05 PTH treatment vs control; b, P<0·05 female control vs male control.

Figure 3

Gender differences in BMSC colony number and ALP activity (Day 14). Results are expressed as mean ±s.d. (A) Colony number and (B) ALP activity (ALP/cell). n=3 in each group. a, P<0·05 PTH treatment vs control.

Figure 4

Gender differences in the response to PTH with respect to mRNA levels of bone formation markers. (A) IGF-1 and (B) IGF-1R. Results are expressed as percentage of female control, all values have been normalized to GAPDH mRNA levels in the same sample. n=3 in each group. a, P<0·05 PTH treatment vs control.

Figure 5

Gender differences in the response to PTH with respect to mRNA levels of OPG and RANKL. Results are expressed as percentage of female control, and all values have been normalized to GAPDH mRNA levels in the same sample. n=3 in each group. a, P<0·05 PTH treatment vs control.