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Biomedical subjects

G Lane

Publications and source records attributed to G Lane.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effects of dydrogesterone on the oestrogenized postmenopausal endometrium.

Postmenopausal women receiving conjugated oestrogens 1.25 mg daily continuously were also given dydrogesterone either 5, 10 or 20 mg daily for the first 12 days of each calendar month. Endometrial tissue obtained on the sixth day of combined therapy in the third or subsequent treatment cycle was subjected to histological, ultrastructural and biochemical assessments. Dydrogesterone provoked secretory histological and ultrastructural changes within the endometrium in a dose-dependent manner. A daily dose of 5 mg produced sub-optimal responses but 10 and 20 mg daily produced effects similar to those observed in the secretory phase of the ovulatory cycle. Dydrogesterone 10 mg and 20 mg daily reduced epithelial DNA synthesis and nuclear oestradiol receptor levels to values within the secretory phase range. A dose-response relation was seen in the induction of oestradiol-17 beta and isocitrate dehydrogenase activities; hyperphysiological values were observed with 20 mg of dydrogesterone daily. This study has demonstrated that dydrogesterone exerts potent anti-oestrogenic and progestational effects on the human endometrium which are dose-related. The 10 and 20 mg doses induced responses equal to or greater than those observed in the secretory phase of the ovulatory cycle and both dosages can be recommended for use in combination with exogenous oestrogens in postmenopausal women: and they may also have a role in the management of anovulatory dysfunctional uterine bleeding.

Cell Nucleus↗
PubMed1986

Oestriol with oestradiol verses oestradiol alone: a comparison of endometrial, symptomatic and psychological effects.

In a prospective, double-blind, randomized, cross-over trial, the effects of oral oestradiol, 2 mg daily, on the endometrial histology, frequency and severity of vaginal bleeding, and the symptomatic and psychological status of postmenopausal women were compared with those of oral oestradiol, 2 mg daily, plus oestriol, 1 mg daily. Both therapies were prescribed for 3 months on a cyclical basis. The addition of oestriol to oestradiol did not modify the endometrial response. The prevalence of proliferative/hyperplastic endometrium (64%: 9 of 14 biopsies) was similar after both treatments and there were no significant differences in either the frequency or heaviness of vaginal bleeding. Both therapies significantly reduced hot flushes, night sweats and vaginal dryness: no significant differences in effect on the symptomatic and psychological status were recorded. The addition of 1 mg of oestriol to 2 mg of oestradiol did not confer any benefit and the value of such an addition is challenged.

Adult↗
PubMed1986

Is Provera the ideal progestogen for addition to postmenopausal estrogen therapy?

In a dose-ranging study, medroxyprogesterone acetate, 2.5, 5, or 10 mg daily, was given for 12 days of each calendar month to postmenopausal women also receiving conjugated estrogens, 0.625 mg daily, continuously. Endometrial biopsy specimens were taken on the sixth day of combined therapy for histologic, ultrastructural and biochemical evaluation. Medroxyprogesterone acetate induced secretory and ultrastructural changes within the endometrium, but the responses were variable and inconsistent. Suppression of epithelial deoxyribonucleic acid synthesis appeared dose-dependent. The levels of nuclear estradiol receptor, although reduced to within the secretory phase range, were not significantly lower than the values observed during the estrogen-only phase of treatment. Induction of both estradiol and isocitrate dehydrogenase activities was to within the secretory phase ranges, but the magnitude of these responses appeared less than those observed previously with other progestogens. Both morphologically and biochemically, medroxyprogesterone acetate, even at high dosage, produced suboptimal responses. Further studies are required to establish whether this is a dose-related effect.

Biopsy↗
PubMed1984

Increased vasoconstrictor activity of proximal coronary arteries with endothelial damage in intact dogs.

In this study we examined the hypothesis that endothelial damage increases proximal coronary arterial vasomotor tone and sensitivity to vasoconstrictor stimulation. The response of the left anterior descending coronary artery (LAD) (% area change) to serotonin and nitroglycerin were examined in eight anesthetized (Innovar + nitrous oxide), closed-chest dogs by means of quantitative coronary angiography. Dose-response curves of percent change in arterial cross-sectional area for three doses of intracoronary serotonin were examined before and after endothelial damage produced by a balloon catheter in the LAD. Endothelial damage was verified by postmortem scanning electron microscopic examination. Intracoronary injection of 133Xe provided coronary flow data. The damaged segment of LAD showed spontaneous vasoconstriction and further constriction in response to serotonin (33 +/- 5% before and 52 +/- 6% area reduction after damage; p less than .05). Nitroglycerin reversed serotonin-induced vasoconstriction in LAD segments without damage but not in the LAD segment with endothelial damage. No significant changes were observed in aortic pressure, and heart rate was kept constant by pacing. Blood flow in the LAD was not affected by endothelial damage itself (control, 2.44 +/- 0.09 ml/min/g; damage, 2.53 +/- 0.22 ml/min/g). Endothelial damage induced spontaneous proximal coronary constriction and diminished the relaxant response to nitroglycerin in the presence of serotonin. These results suggest that focal coronary narrowing that occurs in some patients after provocation with vasoconstrictor agents may be caused by local areas of damaged endothelium.

Animals↗
PubMed1983

Dose dependent effects of oral progesterone on the oestrogenised postmenopausal endometrium.

Oral progesterone 100, 200, or 300 mg daily was given for the first 10 days of each calendar month to postmenopausal women also receiving conjugated oestrogens 1.25 mg daily continuously. Endometrial biopsy specimens were taken on the sixth day of the third or subsequent cycle of combined treatment for histological, ultrastructural, and biochemical evaluation. Secretory histological changes were induced within the endometrium in a dose dependent manner, as were progesterone sensitive ultrastructural features such as nucleolar channel systems, giant mitochondria, and subnuclear accumulations of glycogen. Dose response relations were also observed for suppression of DNA synthesis and nuclear oestrogen receptor, and for induction of the activities of oestradiol and isocitric dehydrogenases. Progesterone administered by mouth clearly provokes an end organ response within the endometrium. Suboptimal effects were observed with the lower doses but progesterone 300 mg daily achieved responses approaching and within the physiological range. This dose may therefore be effective as an alternative to synthetic progestogens for therapeutic purposes.

Dose-Response Relationship, Drug↗
PubMed1983

Regulation of calcium-regulating hormones by exogenous sex steroids in early postmenopause.

A major function of calcitonin in humans appears to be maintenance of the skeleton. There is a marked sex difference in circulating calcitonin levels: women have much lower levels. This has led to speculation that calcitonin lack may be one factor involved in the pathogenesis of postmenopausal bone loss. We have measured levels of calcitonin and the other major calcium-regulating hormones in healthy women during the early menopause, and studied the effects of reversing their oestrogen deficiency with natural and synthetic oestrogen. The major findings were that calcitonin levels were increased by oestrogen administration (P less than 0.02-less than 0.001) and that the levels of the bone-resorbing hormones, parathyroid hormone and 1,25 dihydroxyvitamin D, were not higher in postmenopausal than in premenopausal women. We suggest that loss of oestrogen at the menopause accelerates the natural age-related decline of calcitonin secretion, thus further decreasing the calcitonin levels. This leads to increased sensitivity of the skeleton to the actions of the bone-resorbing hormones. It seems likely that the well-known effect of oestrogen in preventing postmenopausal bone loss is achieved, at least in part, by enhancement of calcitonin secretion.

Adult↗
PubMed1982

Actions of progestins on the morphology and biochemistry of the endometrium of postmenopausal women receiving low-dose estrogen therapy.

Endometrial biopsies were obtained from postmenopausal women receiving 0.625 mg Premarin daily and either 2.5 or 5 mg norethindrone daily or 150 or 500 microgram dl-norgestrel daily for 10 days each month. Sample were taken during the estrogen-only phase of treatment and on the sixth day of combined estrogen/progestin administration. Progestin exposure caused marked morphologic and biochemical changes as well as features comparable with the premenopausal luteal phase. Thus, progestins oppose the stimulation of premarin to the postmenopausal endometrium. However, the currently recommended dosage of norethindrone and dl-norgestrel greatly exceed those necessary to suppress endometrial proliferation effectively. The recommended daily dosage may be lowered without losing protective effect. This reduction will probably minimize the risk of dose-dependent progestin side effects.

DNA↗
PubMed1981

Interrelations of calcium-regulating hormones during normal pregnancy.

Profound changes in calcium metabolism occur during pregnancy. The mother has to make available extra calcium for fetal requirements while ensuring that her plasma and bone calcium concentrations are satisfactorily maintained. In a cross-sectional study plasma concentrations of the major calcium-regulating hormones--namely, calcitonin, parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-(OH)2D)--were measured to establish their interrelations during normal pregnancy. The major changes observed were increases in the circulating concentrations of 1,25-(OH)2D and calcitonin. Concentrations of parathyroid hormone and 25-OHD remained within the normal range. The increased concentrations of 1,25-(OH)2D enable the increased physiological need for calcium to be met by enhancing intestinal absorption of this element. The simultaneous rise in calcitonin opposes the bone-resorbing activities of 1,25-(OH)2D, thereby protecting the integrity of the maternal skeleton. Maternal calcium homeostasis is thus maintained yet the requirements of the fetus are fulfilled.

25-Hydroxyvitamin D 2↗
PubMed1981

Oral progesterone.

Explore the source record for details and available documents.

Administration, Oral↗
PubMed1981

Oestradiol: the predominant intranuclear oestrogen in the endometrium of oestrogen-treated postmenopausal women.

Intracellular oestrogen metabolism has been investigated in endometrial tissue from postmenopausal women receiving oestrogen therapy either alone or in combination with a progestogen. During oestrogen therapy alone, there was a 3.2 fold predominance of oestradiol over oestrone within the endometrial cell nucleus and the mean nuclear oestrogen receptor content was 1.40 pmol/mg DNA. The addition of norethisterone decreased the nuclear oestradiol/oestrone ratio to 1.4:1 by lowering the oestradiol mass. A concurrent reduction in the mean level of the nuclear oestrogen receptor to 0.58 pmol/mg DNA indicated a decrease in oestrogenic stimulation. The activity of oestradiol-17 beta dehydrogenase was significantly increased. There was a plasma excess of oestrone over oestradiol during oestrogen therapy alone and oestrone/oestradiol ratio was not significantly altered following norethisterone administration. The ability of the endometrium to incorporate oestradiol selectively into the nucleus is discussed in relation to the risk of endometrial hyperplasia with unopposed oestrogen therapy. The profound biochemical changes induced by norethisterone help elucidate mechanisms whereby progestogens lower oestrogenic potency and thereby protect the endometrium against excessive stimulation.

Cell Nucleus↗