Abstract

We have recently found that administration of oestradiol-17β (OE₂) to rats stimulates trabecular bone formation. It is not known, however, whether oestrogen has a similar action on bone formation rate under physiological circumstances. Oestrogen is known to suppress bone resorption, and oestrogen-deficient states in the rat, as in humans, are associated with an increase in bone resorption that entrains an increase in bone formation. To see if the latter masks a relative reduction in bone formation, due to oestrogen deficiency, we measured bone formation very early after ovariectomy, before the resorption-induced increase in bone formation becomes established. To do this, rats were administered fluorochrome labels before and after ovariectomy, spaced at weekly intervals in the first, and 3-day intervals in the second experiment.

In both experiments there was a decrease in indices of bone formation in the labelling interval immediately following ovariectomy such that, using the shorter fluorochrome intervals, the mineral apposition rate fell to 69%, the double-labelled surface to 45%, and the bone formation rate to 36% of sham-ovariectomized levels. The reduction was not sustained in the subsequent label intervals, presumably masked by the increase in bone formation attributable to increased resorption. These results suggest that if bone formation is assessed before this resorption-entrained increase in bone formation occurs, oestrogen deficiency is associated with a reduction in dynamic indices of bone formation. Thus, these experiments suggest that oestrogen stimulates bone formation under physiological circumstances, and that the osteopaenia that follows oestrogen deficiency may be attributable not only to an increase in bone resorption, but also to a relative deficiency in bone formation.

Journal of Endocrinology (1994) 142, 119–125

ABSTRACT

Peripheral blood samples were collected at 10-min intervals from three conscious sheep in which ovulation had been induced 6–10 days previously using exogenous hormones. Saline was infused into a jugular vein for about 1 h, followed by the experimental drug for 1–2 h and followed by saline again for a further 2 h. The experiments were repeated following induced luteolysis and ovulation. The infusion of a β-adrenergic antagonist (propranolol) into three conscious luteal-phase ewes decreased (P<0·05) the peripheral progesterone concentration in each animal. Infusions of β₂-adrenergic agonists (ritodrine and salbutamol) increased (P<0·05) the progesterone concentration in four out of eight experiments. The β-adrenergic antagonist decreased the heart rate and the β₂-adrenergic agonist increased it; the arterial blood pressure and respiratory rate were unaffected. The decrease in the prosgesterone concentration in response to the β-adrenergic antagonist suggests that the normal ovarian secretion of progesterone is partly the result of sympathetic stimulation, and that the sympathetic innervation of the ovary may have a physiological role in modulating progesterone secretion.

J. Endocr. (1988) 116, 137–142

ABSTRACT

We have previously demonstrated that administration of oestrogen, at doses sufficient to raise serum concentrations to those seen in late pregnancy, increases trabecular bone formation in the metaphysis of adult rats. To determine whether prostaglandins (PGs), which have been shown to induce osteogenesis in vivo, play a role in the induction of bone formation by oestrogen, 13-week-old female rats were given daily doses of 4 mg 17β-oestradiol (OE₂)/kg for 17 days, alone or with indomethacin (1 mg/kg). The rats were also given double fluorochrome labels and at the end of the experiment tibias were subjected to histomorphometric assessment. Treatment with OE₂ suppressed longitudinal bone growth and increased uterine wet weight, as expected, and neither response was affected by indomethacin. Oestrogen also induced a threefold increase in trabecular bone formation in the proximal tibial metaphysis, which resulted in a substantial increase in trabecular bone volume. As previously observed, the increase in bone formation was predominantly due to an increase in osteoblast recruitment (as judged by an increase in the percentage of bone surface showing double fluorochrome labels), with only a minor increase in the activity of mature osteoblasts (as judged by the mineral apposition rate). Indomethacin abolished the increase in osteoblastic recruitment, but the activity of mature osteoblastic cells remained high. The bone formation rate and bone volume remained similar to controls. The results suggest that PG production may be necessary for the increased osteoblastic recruitment induced by oestrogen, but not to mediate the effects of oestrogen on the activity of mature osteoblasts.

Journal of Endocrinology (1992) 133, 189–195