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Biomedical subjects

G S Pope

Publications and source records attributed to G S Pope.

At least 37 records · Page 2Linked to original sources
PubMed1971

Studies on metabolism of vitamin A. The effect of vitamin A status on the secretion rates of some steroids into the ovarian venous blood of pregnant rats.

1. Rats raised on a vitamin A-deficient diet supplemented with either retinyl acetate or retinoic acid were mated and became pregnant. 2. The rates of secretion of progesterone, 20alpha-hydroxypregn-4-en-3-one, oestradiol-17beta and oestrone into the ovarian-venous blood of rats in these two groups were measured on days 9 and 15 of pregnancy. 3. Rates of secretion of progesterone and 20alpha-hydroxypregn-4-en-3-one, both on days 9 and 15, were lower for the rats given retinoic acid. No such differences were found in ovarian oestrogen secretion. 4. The implications of these results are discussed in the light of the previous demonstration that the activity of ovarian 3beta-hydroxy-Delta(5)-steroid dehydrogenase was markedly less in pregnant rats given retinoic acid.

Animals↗
PubMedDate not supplied

Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines.

This paper addresses the question of whether p-hydroxybenzoic acid, the common metabolite of parabens, possesses oestrogenic activity in human breast cancer cell lines. The alkyl esters of p-hydroxybenzoic acid (parabens) are used widely as preservatives in consumer products to which the human population is exposed and have been shown previously to possess oestrogenic activity and to be present in human breast tumour tissue, which is an oestrogen-responsive tissue. Recent work has shown p-hydroxybenzoic acid to give an oestrogenic response in the rodent uterotrophic assay. We report here that p-hydroxybenzoic acid possesses oestrogenic activity in a panel of assays in human breast cancer cell lines. p-Hydroxybenzoic acid was able to displace [(3)H]oestradiol from cytosolic oestrogen receptor of MCF7 human breast cancer cells by 54% at 5 x 10(6)-fold molar excess and by 99% at 10(7)-fold molar excess. It was able to increase the expression of a stably integrated oestrogen responsive reporter gene (ERE-CAT) at a concentration of 5 x 10(-4) M in MCF7 cells after 24 h and 7 days, which could be inhibited by the anti-oestrogen ICI 182 780 (Faslodex, fulvestrant). Proliferation of two human breast cancer cell lines (MCF7, ZR-75-1) could be increased by 10(-5) M p-hydroxybenzoic acid. Following on from previous studies showing a decrease in oestrogenic activity of parabens with shortening of the linear alkyl chain length, this study has compared the oestrogenic activity of p-hydroxybenzoic acid where the alkyl grouping is no longer present with methylparaben, which has the shortest alkyl group. Intrinsic oestrogenic activity of p-hydroxybenzoic acid was similar to that of methylparaben in terms of relative binding to the oestrogen receptor but its oestrogenic activity on gene expression and cell proliferation was lower than that of methylparaben. It can be concluded that removal of the ester group from parabens does not abrogate its oestrogenic activity and that p-hydroxybenzoic acid can give oestrogenic responses in human breast cancer cells.

Binding, Competitive↗
PubMedDate not supplied

Oestrogenic activity of isobutylparaben in vitro and in vivo.

The alkyl esters of p-hydroxybenzoic acid (parabens) are used widely as preservatives in foods, pharmaceuticals and cosmetics to which the human population is exposed. Recent studies have reported that methylparaben, ethylparaben, n-propylparaben and n-butylparaben all possess oestrogenic activity in several in vitro assays and in animal models in vivo. This study reports on the oestrogenic activity of isobutylparaben in a panel of assays in vitro and in vivo. Isobutylparaben was able to displace [(3)H]oestradiol from cytosolic oestrogen receptor alpha of MCF7 human breast cancer cells by 81% at 100 000-fold molar excess. Using a clonal line of MCF7 cells containing a stably transfected oestrogen-responsive ERE-CAT reporter gene, CAT gene expression could be increased by isobutylparaben such that the magnitude of the response was the same at 10(-5) M isobutylparaben as with 10(-8) M 17beta-oestradiol. Isobutylparaben could also increase expression of the endogenous oestrogen-responsive pS2 gene in MCF7 cells and maximal expression at 10(-5) M isobutylparaben could be inhibited with the anti-oestrogen ICI 182 780. The proliferation of two oestrogen-dependent human breast cancer cell lines MCF7 and ZR-75-1 could be increased with isobutylparaben such that at concentrations of 10(-5) M the proliferation response was of the same magnitude as with 10(-8) M 17beta-oestradiol. Evidence for oestrogen receptor mediation of proliferation effects was provided by the inability of isobutylparaben to influence the growth of oestrogen-unresponsive MDA-MB-231 human breast cancer cells and by the ability of the anti-oestrogen ICI 182 780 to inhibit the isobutylparaben effects on MCF7 cell growth. The proliferation response to 10(-10) M 17beta-oestradiol was not antagonized with isobutylparaben at any concentration from 10(-9) M to 10(-4) M in either MCF7 or ZR-75-1 cells. Finally, subcutaneous administration of isobutylparaben was able to increase the uterine weight in the immature mouse after three daily doses of 1.2 or 12.0 mg per mouse. Previous work using linear-alkyl-chain parabens has shown that oestrogenic activity increases with alkyl chain length from methylparaben to n-butylparaben. The results here show that branching of the alkyl chain to isobutylparaben increases oestrogenic activity beyond that of the equivalent length linear alkyl chain in n-butylparaben.

Animals↗
PubMedDate not supplied

Oestrogenic activity of benzylparaben.

Previous work has demonstrated that the alkyl esters of p-hydroxybenzoic acid (parabens) possess oestrogenic activity, which increases with length of alkyl chain from methylparaben to n-butylparaben and with branching in the alkyl chain from n-butylparaben to isobutylparaben. This study reports on the oestrogenic activity of benzylparaben in a variety of assays in vitro and in vivo. Benzylparaben was able to displace [(3)H]oestradiol from cytosolic oestrogen receptor (ER) of MCF7 human breast cancer cells by 22% at 1000-fold molar excess, by 40% at 10,000-fold molar excess, by 57% at 100 000-fold molar excess and by 100% at 1,000,000-fold molar excess. It was able to increase expression of a stably transfected oestrogen responsive reporter gene (ERE-CAT) in MCF7 cells after 24 h at 10(-5)M/10(-4)M and after 7 days at 10(-6)M/10(-5)M/10(-4)M. Proliferation of MCF7 cells could be increased by 10(-6)M/10(-5)M benzylparaben and this could be inhibited by 10(-7)M pure anti-oestrogen ICI 182,780, indicating that growth effects were ER mediated. Further evidence for ER-mediation was provided from the ability of benzylparaben to increase the growth of a second oestrogen-dependent human breast cancer cell line ZR-75-1, but not the oestrogen-insensitive MDA-MB-231 cell line. When tested in the presence of 10(-10)M 17beta-oestradiol, benzylparaben gave no antagonist response on the growth of either MCF7 or ZR-75-1 cells. Finally, benzylparaben could increase uterine weight in the immature mouse following topical application of three daily doses of 33 mg to dorsal skin. These results demonstrate that the oestrogenicity of methylparaben can be increased by the addition of an aryl group as well as by lengthening or branching the alkyl grouping.

Administration, Topical↗
PubMedDate not supplied

Concentrations of parabens in human breast tumours.

Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.

Breast Neoplasms↗
PubMedDate not supplied

Concentrations of oestradiol-17 beta in plasma and milk and progesterone in plasma during the oestrus cycle and in early pregnancy in goats.

Pre-ovulatory peaks in oestradiol-17 beta concentrations were observed on days 1 or 2 and post-ovulatory peaks between days 4 and 7, both in jugular venous plasma and defatted milk, day 1 being the day of the onset of oestrus in the goats. Mean values of the magnitudes of these concentration peaks and of their timing (relative to oestrus) during the oestrus cycle did not differ significantly (P greater than 0.05) from those when the goats were mated and became pregnant. Pre-ovulatory oestradiol-17 beta peaks were invariably greater than the corresponding post-ovulatory peaks, as were peak concentrations in plasma relative to those in defatted milk collected on the same day. Mean intervals between the pre- and post-ovulatory peaks in oestradiol-17 beta concentrations were respectively 4.2 days for plasma and 4.0 days for defatted milk. Concentrations of oestradiol-17 beta in jugular venous plasma and defatted milk were strongly correlated: rank correlation coefficients for the three goats studied were 0.871, 0.668 and 0.739. It is suggested that in goats, as in cattle, ovarian follicular oestradiol-17 beta secretion approaching pre-ovulatory level is restored by 4 days after oestrus and its rapid decline after this time may be due to the inhibitory influence of the rapidly rising plasma progesterone concentration.

Animals↗
PubMedDate not supplied

The value of progesterone, oestradiol benzoate and cloprostenol in controlling the timing of oestrus and ovulation in dairy cows and allowing successful fixed-time insemination.

The relative merits of three hormone treatments of dairy cows: (1) intravaginally administered progesterone and oestradiol benzoate; (2) intravaginally administered progesterone and injected cloprostenol; and (3) injected cloprostenol; begun 35-75 days after calving and designed to synchronize oestrus and ovulation and allow successful artificial insemination (AI) at fixed times, have been assessed utilizing information from progesterone concentrations in milk. From this it was concluded that 89% of the cows had ovulated one to three times between calving and the beginning of treatment. Treatment (2) was more effective than (1) in synchronizing ovulation. This was due to the fact that when treatments began early in the ovulation cycle, the requirement for a rapidly effective luteolytic agent was provided by cloprostenol but not by oestradiol benzoate. Treatment (2) was also more effective than (3) in synchronizing ovulation. This is interpreted as meaning that progesterone treatment for 12 days had a beneficial effect in restoring normal cyclic ovarian function in the cows after calving. Whilst cloprostenol administered alone did not have this beneficial effect, there is no evidence that it had a detrimental effect. Based on all cows in treatment groups, the proportion that became pregnant to the fixed-time AI was significantly greater after treatment (2) than after (1), but when based on numbers of cows with synchronized ovulation, there were no significant differences among treatments in the proportions becoming pregnant. The progesterone/cloprostenol treatment had a disadvantage in that when begun during the 11-22 day period of the ovulation cycle, so resulting in a long, total period of suppression of ovulation (mean, 32.1 days), fertility to the fixed-time AI was poor despite effective synchronization of ovulation. Ovulation cycles immediately following the failed, fixed-time AI were normal, both in length and in maximum, luteal-phase progesterone concentration and indicated normal corpus luteum function. Thus the infertility could be ascribed neither to poor timing of AI nor to gross degeneration of follicles prior to their synchronized ovulation following the prolonged suppression of ovulation. The 12-day progesterone treatments when given to anovulatory cows gave, within 5.5 h of their beginning, a concentration of progesterone in milk that was not significantly different from the maximum reached. This concentration declined during the 12 days of the treatment but remained above pretreatment level until 5.5 h after treatment withdrawal; the maximum reached was about half that in normal ovulation cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Oestradiol-17 beta in the milk of cows from 6 days before to 14 days after their insemination.

In artificially inseminated cows (AI on day 1) peak concentrations of oestradiol-17 beta in defatted milk occurred at median times of day 0 during the pre-ovulatory period, days -5 to 2, and day 6 during the post-ovulatory period, days 2-15. Median peak concentrations during these periods were approximately 5 pg/ml and 3 pg/ml respectively. There were no significant differences in the timing or magnitude of oestradiol-17 beta concentrations between cows that became pregnant to the AI and those that entered normal length oestrus cycles immediately after AI.

Animals↗