Biomedical subjects

E Norjavaara

Publications and source records attributed to E Norjavaara.

33 records · Page 2Linked to original sources

PubMed1988

Vascular resistance is decreased in the luteal rat ovary by a 20 minute continuous infusion of noradrenaline.

The effect of a 20 min continuous infusion of noradrenaline (2 nanomoles/min) on the blood flow and vascular resistance of 2-, 6- and 11-day-old corpora lutea from adult pseudopregnant rats was studied. Pseudopregnancy was induced by mating with vasectomized male rats. The blood flow of the corpus luteum and the remaining ovary was measured with the microsphere technique. The basal blood flow varied between the luteal ages studied and was highest at day 6 of pseudopregnancy. Noradrenaline induced a two-fold increase in the blood flow of the corpus luteum at the luteal ages studied. The vascular resistance (blood pressure/blood flow) decreased for all luteal ages, while the vascular resistance for kidney, spleen and diaphragm was unchanged. Antidiuretic hormone was found to markedly decrease the luteal blood flow and the vascular resistance remained increased. The effect of noradrenaline infusion on the luteal blood flow thus in contrast to other vasoactive substances is biphasic, with an initial vasoconstriction followed by vasodilatation.

Animals↗

PubMed1987

Catecholamine content and adenylate cyclase activity in corpora lutea of different ages of the PMSG-treated immature rat.

The catecholamine content and adenylate cyclase response were studied in a well-characterized corpus luteum model, where ovulation was induced by treatment of prepubertal Sprague-Dawley rats with pregnant mare's serum gonadotropin. The luteal content of noradrenaline, determined with HPLC, was constant during the first 7 days of pseudopregnancy, followed by a 3-fold increase in older corpora lutea. No detectable amounts of dopamine were found, while trace amounts of adrenaline were found in a few cases. The increase in noradrenaline content was not associated with a changed sensitivity of luteal adenylate cyclase to catecholamines. The response to adrenaline was maximal in 3-day-old corpora lutea, whereafter a decrease was seen. The significance of the increased endogenous levels of noradrenaline at the end of pseudopregnancy is at present unknown. However, the fact that the increase in noradrenaline occurs a few days before spontaneous luteolysis is of special interest, since it has been suggested that an adrenergic innervation is a prerequisite for the antigonadotropic effect of prostaglandin F2 alpha in the human corpus luteum.

Adenylyl Cyclases↗

PubMed1987

Redistribution of ovarian blood flow after injection of human chorionic gonadotropin and luteinizing hormone in the adult pseudopregnant rat.

It is well known that LH and human CG (hCG) induce an increase in total ovarian blood flow. The effect of LH/hCG on luteal blood flow, however, is unknown. This work studies the effect of hCG on both luteal and ovarian blood flows at different stages of pseudopregnancy in adult female rats. Pseudopregnancy was induced by mating with sterile male rats. The length of pseudopregnancy was 13 +/- 1 days and, during this time, blood flow was measured by the injection of radioactive microspheres during anesthesia. At autopsy, the corpora lutea were identified and extirpated under a stereomicroscope. These, and the remaining ovary, were then counted for radioactivity and the blood flow was calculated. Progesterone levels were determined in plasma and ovarian tissues. Furthermore, the responsiveness of adenylate cyclase was tested in ovarian tissues at day 6 of pseudopregnancy. An intraarterial injection of hCG (50 IU) or vehicle (saline) was given 20 min before the blood flow determinations in anesthetized rats. The luteal blood flow was not changed by hCG on days 2, 6, and 11 of pseudopregnancy, whereas in the remaining ovary the blood flow increased more than 2-fold, thereby resulting in redistribution of the blood flow. Ten micrograms of NIH-LH-B9, tested at day 6 of pseudopregnancy, mimicked the effect of hCG. At day 6 of pseudopregnancy, hCG (50 IU) was given ip to conscious rats 200 min and 24 h before blood flow determinations. At 200 min after hCG there was a more pronounced redistribution of ovarian blood flow with a 45% reduction in luteal blood flow and a 4-fold increase in flow through the remaining ovary. LH as well as hCG doubled the progesterone content of the remaining ovary. In the corpora lutea an increased progesterone content was seen after 200 min of hCG exposure. At 24 h after hCG injection, all parameters had returned to control levels except that adenylate cyclase was nonresponsive. The increase in the total ovarian blood flow coincides with the increased steroidogenesis and these effects are likely due to release of metabolites and/or vasoactive substances. Despite this increase, the blood flow of the corpus luteum was not increased rendering vascular mechanisms unlikely as a part of the acute LH/hCG effects on corpus luteum of pseudopregnancy.

Adenylyl Cyclases↗

PubMed1987

Studies of the luteinization process in the rat: follicular and luteal adenylate cyclase responsiveness to catecholamines.

The subject of the study was the development of follicular and luteal catecholamine responsiveness during the periovulatory period. Follicles and corpora lutea and granulosa cells were obtained from the PMSG ovulatory model and adenylate cyclase activity measured in membrane fractions. In the earlier part of the follicular phase (48 h and 26 h before ovulation) no response to noradrenalin on follicular and granulosa cell adenylate cyclase activity was seen. A small but significant response to noradrenalin was observed from 18 h before until 3 h after ovulation. The response to noradrenalin on luteal adenylate cyclase activity increased markedly with time and reached a maximum 39-57 h after ovulation. After this time the luteal response to noradrenalin decreased with luteal age. The effect of LH was less than that of noradrenalin during the early luteal phase, and in contrast to noradrenalin, increased with luteal age. The combined effects of LH and noradrenalin were not additive. In order to test whether gonadotropins could induce a noradrenalin response, injections of LH and FSH were given to the animals two days before ovulation. LH, but not FSH, induced a small but significant response to noradrenalin 16 h later. The present investigation has shown that ovarian responsiveness to catecholamines appears in preovulatory follicles followed by a marked increase in luteal catecholamine responsiveness. This development could at least partly occur under the influence of LH.

Adenylyl Cyclases↗

PubMed1986

Mechanism of action of prostaglandin F2 alpha-induced luteolysis: evidence for a rapid effect on the guanine nucleotide binding regulatory component of adenylate cyclase in rat luteal tissue.

The initial events in prostaglandin F2 alpha-(PGF2 alpha)-induced luteolysis were studied in pregnant mare serum gonadotropin/human chorionic gonadotropin-(PMSG/hCG)-treated rats with luteinized ovaries. Injection with a potent PGF2 alpha analog (cloprostenol, 5 micrograms/ml) induced functional luteolysis, as assessed by plasma levels of progesterone and 20 alpha-dihydroprogesterone. At 0.5 and 3 h after cloprostenol administration the luteolytic effect was also evident as a reduced response of luteal adenylate cyclase to all stimulatory agents tested, LH, isoproterenol, fluoride, guanylylimidodiphosphate and forskolin. 24 h after cloprostenol the response to all agents, except to LH, had returned to normal. This general and transient block of the luteal adenylate cyclase system indicates that a common factor, possibly the stimulatory guanine nucleotide binding protein (Ns), is involved in the mechanism of action of PGF2 alpha. To test this hypothesis, we measured the functional coupling of the Ns protein to the beta-adrenergic receptor in luteal membranes. Binding competition curves showed a marked shift to the right in membranes prepared from rats injected with cloprostenol 0.5 and 3 h before membrane preparation, while at 24 h after cloprostenol the shift had disappeared. The total number of beta-adrenergic receptors was, however, not affected by the cloprostenol treatment. Computer analysis of the data indicates that, at 0.5 and 3 h after cloprostenol treatment, there was a reduced number of high affinity binding sites, 38 and 41%, respectively, compared to 53% for control membranes. The cellular mechanism for this action of PGF2 alpha on the Ns protein remains to be elucidated.

Adenylyl Cyclases↗

PubMed1986

Adenylate cyclase activity in rat corpora lutea evidence for a rapid development of the regulatory Ns-protein.

Adenylate cyclase activity was studied in membranes from isolated corpora lutea of defined ages obtained from pregnant mare's serum gonadotropin treated rats and the effects of luteinizing hormone (LH), isoproterenol, guanylylimidodiphosphate (Gpp (NH)p), fluoride and forskolin were compared. The effect of LH on adenylate cyclase activity increased with the luteal age up to nine days of age, while the effect of isoproterenol increased dramatically during the first days, reaching a maximum at 2-3 days of age and then declined. Forskolin potentiated the effects of both LH and isoproterenol without affecting the patterns of age-dependency. The effect of forskolin itself was fairly constant during the luteal phase, indicating a relatively constant amount of the catalytic unit in the corpus luteum. The effects of fluoride and Gpp(NH)p on the other hand increased markedly during the first days and then remained constant for the rest of the period studied. These results suggest that the regulatory Ns-protein develops during the first days of luteal life. It is speculated that the close correlation between the development of beta-adrenergic response and the development of Ns-protein are causally related.

Adenylyl Cyclases↗

PubMed1985

Partial denervation of the ovaries by transection of the suspensory ligament does not inhibit ovulation in rats treated with pregnant mare serum gonadotropin.

Adrenergic nerves reach the ovary via two routes: along the arteries to the ovary and via the suspensory ligament. Results from earlier investigations suggest that denervation of the nerves along the arteries does not influence the ovulatory process. In the present study we have examined whether denervation by transection of the ovarian suspensory ligament influences the ovulatory process. Partial denervation of the ovary by transection of the ovarian suspensory ligament, sham operation, or only anesthesia were performed on immature 25-day-old rats. To induce ovulation, pregnant mare serum gonadotropin (PMSG) was injected in the morning (0800-0930), when the rats were 26 days old. This PMSG treatment normally induces ovulation around 0200 in the early morning of day 29 with subsequent formation of corpora lutea. Rats were killed 5-8 hr, 3 days, and 5 days after this ovulation time. Ovarian interstitial norepinephrine levels were markedly decreased after transection of the suspensory ligament. Ovulations had occurred in all denervated, as well as sham-operated, and control rats. The various groups did not differ in the number of ovulations per rat. Thus, the adrenergic nerves in the suspensory ligament appear not to be necessary for ovulation. Whether catecholamines themselves play a role in the ovulatory process cannot be elucidated from this experiment, since the norepinephrine content in the ovary was not totally depleted. It seems unlikely that adrenergic nerves reach the corpus luteum via the suspensory ligament, since transection of this structure did not change the luteal content of norepinephrine.

Animals↗

PubMed1985

Acute increase of noradrenaline on vascular resistance in the corpus luteum of the pseudopregnant rat.

Noradrenaline infusion for 2 min (0.4 microgram/min) in anaesthetized rats increased the vascular resistance in 6-day-old corpora lutea, but had no significant effect on the vascular resistance in young (2-day-old) or old corpora lutea (11 days old). The luteal blood flow of the control rats was higher in 6-day-old corpora lutea than in those of 2 and 11 days. The luteal blood flow apparently lacks autoregulation, since a linear relationship between blood flow and arterial blood pressure was registered. The present study shows that, besides the well known metabolic effects of catecholamines on corpus luteum function, catecholamines can exert acute vascular effects, but only on the corpus luteum of pseudopregnancy in the middle of its life span.

Animals↗

PubMed1984

Beta-adrenergic receptor concentration in corpora lutea of different ages obtained from pregnant mare serum gonadotropin-treated rats.

We have measured the beta-adrenergic receptor content in 1- to 10-day-old corpora lutea. Corpora lutea of defined ages were obtained by sc injection of 8 IU PMSG to 26-day-old rats, leading to ovulation and formation of corpora lutea in the early morning of day 29. Membrane fractions of isolated corpora lutea were incubated with various concentrations of the beta-adrenergic antagonist [125I]iodohydroxybenzylpindolol [125I]iodo-HYP, 12.5-2500 pM) for 60 min at 22 C. Alprenolol (10(-5) M) was used to determine nonspecific binding. Bound and free [125I]iodo-HYP was separated by filtration and washing on Whatman GF/C filters under vacuum. There was a 3-fold increase in beta-adrenergic receptor concentration during the first 2-3 days of corpus luteum formation, followed by a decline in the beta-adrenergic receptor content with luteal age. The rat luteal beta-adrenergic receptor seems to be of the beta 2-subtype as determined from adenylate cyclase stimulation as well as from displacement of [125I]iodo-HYP binding by various beta-adrenergic agonists.

5-alpha-Dihydroprogesterone↗

PubMed1983

Prostaglandin F2 alpha inhibition of epinephrine stimulated cyclic AMP and progesterone production by rat corpora lutea of various ages.

Epinephrine can mimic the stimulatory effects of LH in vitro on cyclic AMP (cAMP) and progesterone production by isolated rat corpora lutea. The aim of the present study was to test whether the effects of epinephrine in vitro on the rat corpus luteum, as with LH, can be inhibited by prostaglandin F2 alpha (PGF2 alpha). The stimulatory effect of epinephrine on tissue levels of cAMP in 1-day-old corpora lutea was not inhibited by PGF2 alpha. A dose-dependent inhibition by PGF2 alpha (0.5-50 microM) was seen for 3-day-old corpora lutea and this inhibition could not be overcome by higher concentrations of epinephrine (0.165-165 microM). The stimulation by epinephrine on progesterone production was inhibited by PGF2 alpha (5 microM) in 3- and 5-day-old, but not in 1-day-old corpora lutea. Thus, PGF2 alpha can inhibit the stimulatory effect of epinephrine in 3- and 5-day-old corpora lutea, but not in the newly formed corpora lutea (1-day-old) and PGF2 alpha shows in this respect the same age dependent inhibitory pattern as in relation to LH stimulation.

Aging↗

PubMed1983

Development of catecholamine responsiveness in granulosa cells from preovulatory rat follicles--dependence on preovulatory luteinizing hormone surge.

Factors responsible for development of catecholamine (CA) responsiveness in granulosa cells (Gc) of preovulatory follicles from immature rats injected with 10 IU of pregnant mare's serum gonadotropin (PMSG) on Day 26 were studied. CA did not stimulate cyclic AMP (cAMP) production in whole follicles isolated before (morning) or after (evening) the preovulatory gonadotropin surge on Day 28, while newly formed corpora lutea found on Day 29 responded to CA. Gc from the preovulatory follicles did not respond to CA when tested immediately after isolation. Gc were cultured for various periods in Eagle's MEM without serum and subsequently tested for a possible stimulation of cAMP and steroidogenic responses by CA. In Gc from follicles isolated in the morning (AM-Gc) and cultured for 12 or 24 h, no response to CA was found, while the Gc isolated in the evening (PM-Gc) and cultured similarly for 12 h showed a marked response to CA both in stimulation of cAMP and progesterone production. By a total or partial elimination of the gonadotropin surge, using pentobarbital in combination with luteinizing hormone (LH) or using specific antisera to LH or follicle-stimulating hormone (FSH), it was found that previous exposure to LH was necessary for the PM-Gc to develop CA responsiveness during culture. Further, it was possible to induce CA responsiveness in AM-Gc by treatment of rats with LH for a short period in vivo followed by a period of culture. The appearance of CA responsiveness in PM-Gc cultured for 12 h was abolished when cycloheximide (5 micrograms/ml) was present during culture. It appears that the following three conditions have to be satisfied for the isolated Gc to develop CA responsiveness: 1) exposure to LH in vivo, 2) culture for a short period, and 3) an active protein synthesis. It is concluded that under physiological conditions the process of luteinization is associated with acquisition of responsiveness to CA and this process depends on the LH component of the preovulatory gonadotropin surge.

Animals↗

PubMed1983

In vivo effect of noradrenaline on the cyclic AMP level in rat corpora lutea.

Under in vitro conditions adrenaline and noradrenaline can stimulate the production of cyclic AMP in rat corpora lutea to a similar extent as a maximal dose of LH. The present study was undertaken to compare the effects of noradrenaline and LH under in vivo conditions. Anaesthetized rats bearing 2 days old corpora lutea were either infused intraarterially with noradrenaline (0.4 microgram/min) or given a single intraarterial injection of 5 micrograms LH. The cAMP levels in whole ovaries had increased already after 30 sec of noradrenaline infusion. These levels remained high for a few minutes and, thereafter the effect decreased with time. No effect was seen after 20 min of infusion. Infusion of noradrenaline for 20 min increased cAMP in corpora lutea, but not in non-luteal tissue. LH was effective both in luteal and non-luteal tissue. The results show that noradrenaline in vivo can increase the cAMP content only in corpus luteum and within a rather short time period (5 min). This effect is different from that seen with LH which, instead, acts on both corpus luteum and stromal tissue.

Animals↗

PubMed1982

Catecholamine stimulation of cyclic AMP and progesterone production in rat corpora lutea of different ages.

In vitro effects of catecholamines (adrenaline and noradrenaline) and adrenergic antagonists on adenosine 3',5'-cyclic monophosphate (cAMP) and progesterone production by rat corpora lutea (CL) of different ages (1-8 days old) were studied. To obtain defined ages of CL a pregnant mare's serum gonadotrophin (PMSG) model was used. The effect of catecholamines on cAMP decreased with luteal age while the effect on progesterone production was maximal on 5 day old CL. The beta-blocker propranolol inhibited the effects of catecholamines in concentrations around 10-(5) M. The effects of LH could only be inhibited with higher doses of propranolol known to exert unspecific effects. These results support the theory that LH and catecholamine effects on rat corpora lutea are mediated through different receptors.

Age Factors↗

PubMedDate not supplied

Adult height in women with childhood asthma--a population-based study.

PURPOSE: To study adult height in children that grew up with asthma before inhaled steroids became first-line therapy. METHODS: Data from the Swedish Medical Birth Register (self-reported asthma) and the Hospital Discharge Register (first hospitalization for asthma) were used, to compare adult height for asthmatic and non-asthmatic pregnant women. The analysis was restricted to women in their first full-term pregnancy, born in Sweden between 1960-1974 and of Swedish citizenship. RESULTS: The mean height of all the women in the study population was 166.7 cm (SD = 8.8, n = 287,750) and of the women who reported asthma 166.5 cm (SD = 6.1, n = 13,059, p < 0.01). The mean height of women first hospitalized because of asthma at age 0-8 years was 165.5 cm (SD = 5.9 cm, n = 555, p < 0.01). Among the asthmatic women, there was no skew distribution of heights. CONCLUSIONS: Girls with moderate to severe childhood asthma who grew up before inhaled glucocorticosteroids became first-line therapy attained 0.7-1.2 cm lower adult height. The differences in height. while of statistical relevance, are not clinically relevant.

Adult↗

PubMedDate not supplied

In vivo levels of prostaglandin F2 alpha, E2 and prostacyclin in the corpus luteum of pregnant and pseudopregnant rats.

Prostaglandin F2 alpha (PGF2 alpha) is a well-known luteolytic factor in the rat corpus luteum. To investigate a possible luteal origin of PGF2 alpha, measurements of this prostaglandin were performed in different luteal tissues in vivo. Prostaglandin E2 (PGE2) and the stable metabolite of prostacyclin, 6-keto-PGF1 alpha, were assayed simultaneously. Corpora lutea of different ages from 57 pregnant and pseudopregnant rats (mated with sterile males) were rapidly excised, dissected in 0 degree C indomethacin solution, homogenized, and extracted for prostaglandins with solid-phase extraction cartridges. Prostaglandins were determined by radioimmunoassay. Plasma levels of progesterone and 20 alpha-dihydroprogesterone were also monitored. In the adult pseudopregnant rat model, luteolysis occurs at Day 13 +/- 1, and maximal levels of all three prostaglandins were detected on Day 13 of pseudopregnancy: 0.40 +/- 0.02, 2.6 +/- 0.29, and 1.76 +/- 0.24 pmol/mg protein (mean +/- SEM, n=7) for PGF2 alpha, PGE2, and 6-keto-PGF1 alpha respectively. In pregnant rats, on the corresponding day, levels were considerably lower: 0.15 +/- 0.02, 0.90 +/- 0.13, and 0.50 +/- 0.06 pmol/mg protein (mean +/- SEM, n=9, p less than 0.0001), respectively. Luteal levels in pregnant rats showed a continuous decline on Days 13 and 19 for all prostaglandins measured, whereas in pseudopregnant rats an increment of PGF2 alpha was noted between Days 7 and 13 and remained high on Day 19. PGE2 closely followed levels of PGF2 alpha, but at a 5- to 10-fold higher level. The coefficient of correlation between PGF2 alpha and PGE2 in the luteal compartment of both models was 0.87 (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗