Effect of the Acetophenone-Derivative of 16 ,17 -Dihydroxyprogesterone (Deladroxone) and Estrogen (Dihydroxyprogesterone-acetophenide) on 85Sr Retention in Rats and Mice

Simmons, David J.; Cummins, H.T.

doi:10.3181/00379727-128-33205

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…Erlik et reported a reduction in the Ca/Cr ratio in a small group of postmenopausal women treated with 80 mg MA but could not demonstrate any effects on indices of resorption at lower dose levels. Consistent with our results, however, 16a, 17a-dihydroxyprogesterone and progesterone, two gestagens that are structurally related to MA, have been shown to decrease trabecular bone volume in the proximal tibiae of mice (34) and rats, (35) respectively. Although trabecular bone volumes were not quantitated in this investigation, the possibility that MA reduces 3H-T levels in the tibiae by increasing bone turnover is supported by a study that demonstrated that the gestagen medroxyprogesterone acetate activates cortical bone remodeling and increases bone turnover in spayed beagle dams.…”

Section: Discussionsupporting

confidence: 88%

High-Dose gestagens modulate bone resorption and formation and enhance estrogen-induced endosteal bone formation in the ovariectomized mouse

Bain¹,

Jensen²,

Celino³

et al. 1993

Journal of Bone and Mineral Research

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To determine if gestagens of two separate classes have differing skeletal actions, we studied the effects of pharmacologic doses of norethisterone acetate (NETA), a 19-nortestosterone, and megestrol acetate (MA), a 17 alpha-hydroxyprogesterone, on bone formation and resorption in intact and in ovariectomized mice. In the same set of experiments, we also attempted to determine if these gestagens can alter the skeletal activity of 17 beta-estradiol (E2). Experimentally, the skeletons of 78 female BALB/c mice were prelabeled with [3H]tetracycline (3H-T). The animals were randomized to 13 groups of 6 mice each 3 days after the final 3H-T injection. Ovariectomies (OVX) were performed on 8 groups and sham operations (SO) on 5 groups. To study the skeletal effects of the gestagens, 4 groups each of the OVX and SO mice were treated with controlled-release pellet implants calculated to deliver 80 or 250 micrograms of NETA or MA per day. To study gestagen interactions with E2, 3 groups of OVX mice were treated with either 40 micrograms/day of E2 or 40 micrograms/day of E2 plus 250 micrograms/day of NETA or MA. One group of OVX and one group of SO animals received placebo pellets. Fluorochrome labels were administered 10 and 11 and 3 and 4 days before sacrifice to allow histomorphometric evaluation of bone formation. At the end of the 60 day protocol, tibiae and thoracic vertebrae were removed and processed for quantitating the levels of bone resorption based on the amounts of 3H-T retained in the bones. The femora were fixed and embedded for comparison of diaphyseal bone histomorphometry, and the humeri and lumbar vertebrae were prepared for bone density determinations. Reflecting an increase in bone resorption, 3H-T levels in tibiae and vertebrae were decreased in placebo-treated OVX animals compared to the placebo-treated SO group (p < 0.01). Treatment of both SO and OVX mice with NETA decreased bone resorption in a dose-dependent manner, but MA had no significant effects on vertebral bone resorption and increased bone resorption in the tibiae (p < 0.01). E2 treatment of OVX mice reduced bone resorption, but there were no significant interactions between the E2 and gestagen treatments on resorptive activity. Based on bone histomorphometry of in vivo fluorochrome labels, both gestagens increased periosteal bone formation rates but had no effect on endosteal bone formation (BFRe). In contrast, E2 treatment of the OVX mice stimulated bone formation at the endosteal surface.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionsupporting

confidence: 88%

High-Dose gestagens modulate bone resorption and formation and enhance estrogen-induced endosteal bone formation in the ovariectomized mouse

Bain¹,

Jensen²,

Celino³

et al. 1993

Journal of Bone and Mineral Research

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“…The progesto gen apparently increased periosteal new bone formation without reducing bone resorption, and ash and calcium contents of femora increased significantly during progestogen therapy. In con trast, mice treated with a pure progestogen showed no effect on bone mineral retention, and their tibias showed histological evidence of loss of trabecular bone (Simmons & Cummins, 1968). This may be an example of difference in species sensitivity and it is therefore important to examine critically the effects of similar therapy in the human.…”

Section: Discussionmentioning

confidence: 94%

Comparative Effects of Oestrogen and a Progestogen on Bone Loss in Postmenopausal Women

et al. 1978

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1. The value of progestogen therapy in the prevention of postmenopausal bone loss was assessed in 30 women, by a preliminary randomized controlled trial of gestronol or mestranol, in comparison with a placebo. 2. When the skeletal response was measured by photon absorptiometry, bone mineral loss was prevented by both the oestrogen and the progestogen. 3. We confirm that mestranol significantly reduced the urinary output of hydroxyproline-containing peptide, but this did not occur during gestronol therapy, suggesting that progestogen has a different action on bone, perhaps stimulating bone formation.

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Comparative Physiology of Bone

Simmons¹

1976

Calcification and Physiology

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Effect of the Acetophenone-Derivative of 16 ,17 -Dihydroxyprogesterone (Deladroxone) and Estrogen (Dihydroxyprogesterone-acetophenide) on 85Sr Retention in Rats and Mice

Cited by 4 publications

References 6 publications

High-Dose gestagens modulate bone resorption and formation and enhance estrogen-induced endosteal bone formation in the ovariectomized mouse

High-Dose gestagens modulate bone resorption and formation and enhance estrogen-induced endosteal bone formation in the ovariectomized mouse

Comparative Effects of Oestrogen and a Progestogen on Bone Loss in Postmenopausal Women

Comparative Physiology of Bone

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