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Biomedical subjects

G Selstam

Publications and source records attributed to G Selstam.

At least 73 records · Page 4Linked to original sources

Effects of sex hormone binding globulin capacity and pregnancy zone protein of treatment with combinations of ethinyl-oestradiol and norethisterone.

Sex hormone binding globulin (SHBG) and pregnancy zone protein (PZP) are two highly oestrogen-inducible serum proteins. SHBG capacity and PZP level were measured in 49 women treated with three different combinations of ethinyloestradiol and norethisterone. SHBG capacity and PZP were measured before and after 6 mth of treatment and both serum factors significantly increased during treatment for all three groups. PZP induction was found to be more sensitive and mainly to reflect the oestrogen component of a combined preparation while SHBG capacity was more sensitive to the modulating effect of the progestogen.

Dose-Response Relationship, Drug↗

Effects of various oestrogens on circulating androgens and cortisol during replacement therapy in post-menopausal women.

The influence of various oestrogens during unopposed replacement therapy on circulating androgens and cortisol was studied in 65 post-menopausal women. As dose dependent decrease in dehydroepiandrosterone sulphate (DHAS) was found. Ethinyloestradiol (0.05 mg daily) already gave a significant decrease after 1 mth of treatment. The decline following 17 beta-oestradiol (2 mg) and oestrone sulphate (2.5 mg) was less pronounced. Oestriol (6 mg daily) had no effect. Ethinyloestradiol also increased the levels of total cortisol and testosterone, probable because of serum protein induction, while 17 beta-oestradiol had no significant effect. Serum levels of androstenedione remained unchanged during therapy.

Aged↗

Luteal blood flow and plasma steroids in rats with corpora lutea of different ages.

Ovarian and luteal blood flow rates were measured at different stages of luteal development in anaesthetized rats using 15 +/- 5 micron radioactive microspheres. Ovulations were induced by injection of 8 IU of PMSG at 28 days of age. Steroid concentrations in peripheral plasma were determined using radioimmunoassays. The highest luteal blood flow was found in the youngest corpora lutea and decreased gradually with luteal age. Luteal flow on days 13 and 14 was significantly lower than that of days 2, 4, and 6. Ovarian stromal blood flow remained unchanged throughout the lifespan of the lupus luteum. Peripheral progesterone concentrations rose significantly on days 4, 6, and 8 with a maximum on day 8, as compared to day 2, and fell significantly after day 8. The levels of 20 alpha-OH-progesterone increased sharply on day 10, indicating that functional luteolysis. The progesterone levels fell significantly between day 8 and 10 without a concomitant significant decline in luteal blood flow. Since a fall in progesterone production seem sto precede a drop in luteal blood flow, the initiation of luteolysis does not appear to be caused by a vascular mechanism.

Algestone↗

Different patterns of cyclic AMP accumulation in rat corpora lutea after LH stimulation in vitro and in vivo.

Tissue levels of cyclic AMP were measured in rat corpora lutea at various times after administration of LH in vitro and in vivo. In-vitro addition of LH produced more pronounced accumulation of cyclic AMP in very young corpora lutea (1-day-old) than in the older corpora lutea (3- and 7-day-old). When LH was administered in vivo the highest accumulation of cyclic AMP was seen in the older corpora lutea (7- and 3-day-old).

Animals↗

Nutrition of the intervertebral disc: solute transport and metabolism.

The metabolism of the canine nucleus pulposus was investigated at different oxygen tensions. It was found that even at high oxygen tensions the metabolism is mainly anaerobic, only approximately 1.5% of the glucose being converted to carbon dioxide. The concentration dependence of oxygen consumption is limited to very low oxygen tensions. Values of oxygen consumption and lactic acid production were used to calculate the concentration profiles of these substances within the nucleus pulposus, using a diffusion theory. The predicted concentration profiles were compared with the experimental measurements of concentration at various positions in the disc. The good agreement in these values found in the nucleus confirms that the main mechanism of metabolite transport is diffusion, and the main route of nutrient supply into the nucleus is via the endplate.

Anaerobiosis↗

Hormonal and cellular interactions in follicular steroid biosynthesis by the sheep ovary.

Studies of isolated cell types from sheep follicles revealed several functional changes which occur during follicular maturation. Cyclic AMP production by granulosa cells from the smallest follicles studied (1-3 mm diameter) was stimulated by FSH but not by hCG, suggesting functional FSH receptors at this early stage of differentiation. Medium-sized follicles (4-6 mm) responded to both FSH and hCG. Granulosa cells were unable to synthesize androgens, but readily converted exogenous testosterone to oestradiol-17 beta. This conversion occurred to a limited extent in the cells from the smallest follicles, but was much greater in medium and large (greater than 6 mm) follicles. Oestradiol production by theca preparations from small follicles was barely detectable, but increased markedly with increasing follicle size. Androgen (androstenedione and testosterone) production by theca preparations was stimulated by hCG. This stimulation was short-lived, and levels declined to below control values after 6 h of culture. This decline could not be prevented by addition of cyclic AMP. The presence of granulosa cells with thecal preparations (i.e. follicle wall tissue) enhanced production of androgen by the theca, the effect being more marked for testosterone than for androstenedione. In-vivo studies in which granulosa cells and follicular fluid were removed during the preovulatory period suggested that granulosa cells and/or follicular fluid contributed to the oestradiol secreted into the ovarian vein during this period, but did not exclude a significant contribution by the theca as well.

Androgens↗

Prostaglandin-like substances in Propionibacterium acnes II. Stimulatory effect on ovarian cyclic AMP.

The prostaglandin-like substances (PLS) from Propionibacterium acnes increased the ovarian tissue levels of cyclic AMP (cAMP) approximately 2-fold. The lipid material extracted from P. acnes thus behaved like PG's of the E-type, and since it is unlikely that other known stimulators of the ovarian cAMP system can be present in the bacterial lipid fraction, these experiments give further evidence in favour of the occurrence of PLS in P. acnes.

Animals↗

Lack of specific prostaglandin antagonistic effects of 7-oxa-13-prostynoic acid on ovarian metabolism in vitro.

Prostaglandins (PGs) have been proposed to function as obligatory intermediates in the action of luteinizing hormone (LH) (Kuehl et al. 1970). This based on experiments on isolated mouse ovaries where the substance 7-oxa-13-prostynoic acid (7-oxa-13-PA) was found to block the effect of both PGE1 and LH on ovarian cyclic AMP formation and progesterone synthesis. We have studied whether 7-oxa-13-PA acts as a PG antagonist also on the isolated rat ovary, where PGs of the E type have many effects. Prepubertal rat ovaries were incubated up to 4 h in modified Krebs bicarbonate buffer containing glucose with PGE1 and 7-oxa-13-PA, alone and in combination. PGE1 stimulated the uptake of the non-utilizable amino acids alpha-aminoisobutyric acid (AIB) and cycloleucine in an equally wide dose-range as has earlier been found for the stimulation of lactic acid and cyclic AMP production as well as protein synthesis. 7-oxa-13-PA alone, in concentrations exceeding 25 microgram/ml, stimulated lactic acid production, but inhibited the incorporation of labelled leucine and the uptake of AIB. The uptake of cycloleucine was slightly stimulated. 7-oxa-13-PA did not antagonize the PGE1 effect on lactic acid production. 7-oxa-13-PA diminished the PGE1 effect on the uptake of amino acids and the incorporation into protein, but only in concentrations where it in itself inhibited the protein synthesis. These results show that 7-oxa-13-PA does not act as a PG-antagonist in the prepubertal rat ovary, since it cannot block the effects of PGs without having marked inherent effects.

Amino Acids↗

Differences in action of LH and FSH on the formation of cyclic AMP in the prepubertal rat ovary.

The actions of LH (NIH-LH-B8) and FSH (NIH-FSH-S9) on the cyclic AMP (cAMP) system in ovaries of 23-24 day old rats have been analyzed. An intravenous injection of LH increased ovarian cAMP levels in vivo after only 20 seconds. Maximal cAMP levels were seen after 15 min. Addition of LH or FSH in vitro to the isolated ovaries produced dose dependent increases of cAMP in the tissue as well as in the incubation medium. Low concentrations of LH caused a release of cAMP into the incubation medium without any detectable change in the tissue levels. The levels of cAMP in the incubation media for all concentrations of FSH were lower than the tissue levels, whereas for LH the opposite was found. In time-course experiments where the concentrations of LH (10 mug/ml) and FSH (100 mug/ml) were chosen to give similar tissue levels of cAMP, the release of the cyclic nucleotide into the incubation medium was approximately 2-3 times greater for LH than for FSH at the time periods studied (5-240 min). When LH and FSH were tested together in high concentrations, their effects were additive. When the ovaries were first incubated with FSH for 120 min followed by an incubation with LH, the stimulatory effect of LH was considerably reduced. When the order of the incubations was reversed, however, LH did not change the response to FSH. The results show that both LH and FSH have intrinsic effects on the cAMP system in the prepubertal rat ovary, but that the effects of the two gonadotrophins are not identical.

Animals↗

Stimulatory effect of FSH in vitro on the extracellularly active cyclic AMP phosphodiesterase in the prepubertal rat ovary.

Intact prepubertal rat ovaries were incubated with radioactively labelled adenosine 3',5'-cyclic monophosphate (cAMP) in Krebs bicarbonate buffer containing glucose. The rate of degradation of cAMP was determined by measuring the radioactivity in the medium after precipitation with Ba(OH)2 and ZnSO4. The fate of the nucleotide was followed by measuring the products in the incubation medium. Paper chromatography was used for the separation and identification of these products. It was found that cAMP was degraded to AMP, which in turn was degraded to inorganic phosphate (Pi) and adenosine. An uptake of labelled products was also observed. NIH-FSH-S9 (10 and 100 mug/ml), but not NIH-LH-B8 (0.1-100 mug/ml), increased the degradation of cAMP. Concomitantly, an increased accumulation of labelled adenosine and Pi as well as an increased uptake of labelled products were seen. Kinetic studies with low concentrations of cAMP (0.125-0.025 mumol/l) revealed an apparent Km value of 0.12 mumol/l for the phosphodiesterase (PDE) activity. FSH significantly changed the slope of the curve in the Lineweaver-Burk plot by increasing the PDE activity. The increased PDE activity in the presence of FSH is discussed in relation to earlier findings of differences in action betweeh LH and FSH on the cAMP system in the prepubertal rat ovary.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effect of LH on the release of cyclic AMP by the rabbit ovary perfused in vivo and in vitro.

After perfusion of 10 rabbit ovaries in vitro with a modified Krebs bicarbonate buffer containing dextran and glucose, the concentration of cAMP in the perfusion medium was significantly increased 2-5 min after stimulation with 10 mug LH/ml medium and was higher at 15 and 30 min. Intravenous injection of 100 mug LH/rabbit caused a significant increase of cAMP concentrations in the ovarian venous blood from 8 ovaries 10 min after the injection and the cAMP concentrations were higher after 15 and 30 min. The ovarian blood flow was not changed after the LH injection. It is concluded that perfusion techniques can be useful in analysis of the mechanisms and physiological significance of release of cAMP from the ovary after hormonal stimulation.

Animals↗

A comparison between direct and indirect measurements of blood flow in the follicular ovary of the rabbit.

A comparison was carried out between direct and indirect measurements of blood flow in follicular ovaries of anaesthetized laparotomized rabbits: Direct measurements by timed quantitative sampling of ovarian venous blood yielded blood flow values 3 times higher than those found with the use of 15 mugm radioactive microspheres. However, when simulating the surgical trauma associated with direct measurements, the microsphere technique gave the same high ovarian flow values, indicating that this type of trauma caused ovarian hyperemia. It is concluded that direct measurements of blood flow, as performed in the present study, are unsuitable for investigations of circulatory events in the ovary. Mechanically induced ovarian vasodilatation is probably a factor which helps to explain the diverging data on blood flow obtained with direct and indirect methods. The radioactive microsphere technique appears to provide a means for reasonably reliable ovarian blood flow measurements in laboratory animals.

Animals↗

Characterization of the metabolism of exogenous cyclic AMP by perfused rat heart and incubated prepubertal rat ovary.

In order to study the metabolism of extracellular 3',5'-adenosine monophosphate (cAMP), rat hearts were perfused and prepubertal rat ovaries incubated with 3H- and 32P-labelled cAMP (0.025-1 muM). The rate of disappearance of cAMP from the medium was determined by "Ba-Zn-precipitation" and degradation products of 3H- and 32P-CAMP by paper chromatography. Both tissues degraded cAMP to 5'-adenosine monophosphate (AMP), but the enzyme kinetic for this phosphodiesterase activity was different (apparent Km value for the heart 3.95 muM and for the ovary 0.2 muM). AMP was further degraded, since also other labelled substances were found in the medium. An uptake of both 3H- and 32P-labelled substance(s) into the heart and the ovary was noticed. Tissue extracts contained several labelled purines, but the amounts of labelled cAMP did not exceed expected amounts in the extracellular space. In the ovary the uptake of cAMP and AMP seemed to be low, since the uptake of labelled substances was inhibited by high concentrations of unlabelled AMP or adenosine. The degradation of 32P-cAMP was unchanged when AMP was present, strongly suggesting that the phosphodiesterase enzyme was acting extracellularly. In the heart added AMP was very rapidly degraded making it impossible to elucidate whether cAMP was degraded extracellularly or not. It is concluded that elimination of extracellular cAMP under physiological conditions can be due to degradation of cAMP by various tissues. At least for the ovary this phosphodiesterase enzyme is extracellularly active.

Adenine↗

Effects of LH and HCG on the metabolism of the prepubertal rat ovary: stimulation of amino acid transport, protein synthesis, and glycolysis.

It has earlier been reported from this laboratory that FSH can stimulate amino acid uptake, protein synthesis and glycolysis in the isolated prepubertal rat ovary. In the present investigation to the effects of LH and HCG were studied. The hormones were injected to prepubertal female rats, and the ovaries were extirpated for incubation in Krebs bicarbonate buffer 120 min later. Injected of 1 mu g/100g body weight of a bovine LH preparation (NIH-LH-B8) produced a significant increase in the in vitro uptake of (14C) alpha-amino-isobutyric acid (14C)AIB) and (3H)leucine as well as of the incorporation of radioactivity into the ovarian protein. Higher doses (10 and 100 mu g) of NIH-LH-B8 gave only minor futher increases. Lactic acid production during the incubation period was also measured as a determination of the rate of glycolysis. Lactic acid production was stimulated by the LH injections with a clear dose-response between 0.1 and 10 mu g/100 g body weight. The effects of LH were also investigated with shorter intervals between the injection of the hormone and the extirpation of the ovaries. While lactic acid production was maximally stimulated at a time interval of 30 min (the shortest time interval studied), 60 min was necessary for the stimulation of amino acid uptake and amino acid incorporation into protein. Injections of HCG mimicked the effects of LH on all parameters studied.

Aminoisobutyric Acids↗