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

The effects of thyrotrophin, hypophysectomy, and chronic treatment with thyroxine and methimazole on radioiodide uptake (thyroid/plasma (T/P) ¹²⁵I⁻ ratio), protein and DNA contents and activities of Na⁺,K⁺ -ATPase, HCO⁻ ₃-ATPase, and carbonic anhydrase (CA) of rat thyroid gland were evaluated. Thyrotrophin given to intact rats slightly increased thyroid iodide uptake, did not affect protein or DNA content, and slightly inhibited CA activity (units/g cell water). Hypophysectomy markedly decreased T/P ¹²⁵I⁻ ratio, increased protein content, decreased activity of Na⁺,K⁺-ATPase, and slightly increased HCO⁻ ₃-ATPase (nmol/mg DNA per min) and CA (units/g cell water) activities. Thyro-trophin given to hypophysectomized rats (as compared with untreated hypophysectomized control animals) markedly increased T/P ¹²⁵I⁻ ratio, slightly decreased protein content and decreased Na⁺,K⁺-ATPase and CA activities. Chronic treatment with methimazole increased T/P ¹²⁵I⁻ ratio, decreased protein content, markedly increased Na⁺,K⁺-ATPase and HCO⁻ ₃-ATPase activities, and decreased CA activity. Chronic treatment with thyroxine, in contrast, decreased T/P ¹²⁵I⁻ ratio, decreased Na⁺,K⁺-ATPase activity, and increased CA activity. There was a significant inverse correlation between T/P ¹²⁵I⁻ ratio and CA activity in follicular cells for the various induced functional states of the thyroid.

The effects of acute (200 mg/kg) and chronic (20 mg/kg per day for 7 days) administration of acetazolamide on iodide transport, electrolyte distribution, and on carbonic anhydrase (CA), Na⁺,K⁺-ATPase and HCO₃ ⁻-ATPase activities were evaluated in mouse thyroid glands. The effects of withdrawal from chronic administration of acetazolamide were also assessed. A single injection of a large dose of acetazolamide increased iodide uptake and completely inhibited CA activity. Chronic administration of acetazolamide only slightly increased iodide uptake; CA inhibition was also less marked than after acute administration. After withdrawal of acetazolamide, iodide uptake decreased and CA activity recovered rapidly to the control levels. Chronic treatment with acetazolamide decreased the content of water and increased the contents of protein and DNA in thyroid tissues. Withdrawal of the drug resulted in an increase in Na⁺ and K⁺ contents and a decrease in water content of this gland. These data demonstrate that CA activity has an inverse relation to the iodide transport and a direct relation to Cl⁻ content in the thyroid. Chronic administration of acetazolamide also increased iodide uptake by the thyroid glands of hypophysectomized rats and of turtles.

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