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Biomedical subjects

G Selstam

Publications and source records attributed to G Selstam.

At least 37 records · Page 2Linked to original sources

Effects of acute intravenous injection of two growth hormone-releasing hormones (GHRH 1-40 and 1-29) on serum growth hormone and other pituitary hormones in short children with pulsatile growth hormone secretion.

We administered two different growth hormone-releasing hormones (GHRH) to 20 short, prepubertal children who had spontaneous secretion of growth hormone (GH), assessed from 24-hour GH secretion profiles (72 sampling periods of 20 min). We compared one i.v. injection of 1 microgram/kg of GHRH 1-40 with that of GHRH 1-29 regarding serum concentrations of GH, prolactin, luteinizing hormone, follicle-stimulating hormone and IGF-I. The children were allocated to two groups without statistical randomization. Both groups were given both peptides, with at least 1 week in between. The first group started with GHRH 1-40, the other with GHRH 1-29. The peptides both induced an increased serum concentration of GH of the same magnitude: mean maximal peak of 89 +/- 12 mU/l after GHRH 1-40 and 94 +/- 10 mU/l after GHRH 1-29 (n.s.). The mean difference in maximum serum GH concentration in each child after injection was 52 +/- 9 mU/l, range 1-153 mU/l. GHRH 1-29 also induced a short-term, small increase in the concentrations of prolactin (p less than 0.05), luteinizing hormone (p less than 0.01) and follicle-stimulating hormone (p less than 0.05). We conclude that the shorter sequence GHRH 1-29, when given in a dose of 1 microgram/kg, gives a rise in serum concentration of GH similar to that after the native form GHRH 1-40.

Adolescent↗

Beta-adrenergic receptor concentration and subtype in the corpus luteum of the adult pseudopregnant rat.

Luteal beta-adrenergic receptor concentration and subtype were determined in adult pseudopregnant rats during and after the period of the functional luteal phase. The specific beta-adrenergic receptor ligand (-)-3-[125I]iodocyanopindolol ([125I]ICYP) was used to determine the receptor concentration in corpora lutea of adult pseudopregnant rats. A 3-fold increase in beta-adrenergic receptor concentration was seen during the first 2-3 days of pseudopregnancy, whereafter the receptor concentration declined. During the functional luteal regression period (Day 12-15) the receptor levels were still low. In regressed (Day 16-22) corpora lutea a temporary increase in beta-receptor concentration was seen which may represent some role for beta-adrenergic mechanisms in the regulation of morphological regression in the corpus luteum. To determine the beta-adrenergic subtype, competition of [125I]ICYP-binding with selective beta 1- and beta 2-adrenergic antagonists was assessed in corpora lutea of different ages and in rat heart and uterus. The beta-adrenergic receptors in corpora lutea of adult pseudopregnant rats were shown to be solely of the subtype beta 2, regardless of the luteal age.

Animals↗

Changes in corpus luteum content of prostaglandin F2 alpha and E in the adult pseudopregnant rat.

Conflicting reports exist regarding the source of luteolytic PGF2 alpha in the rat ovary. To assess the quantities of different PGs, measurements of PGF2 alpha, PGE and PGB were performed by radioimmunoassay in the adult pseudopregnant rat ovary throughout the luteal lifespan. Ovaries of 84 rats were separated by dissection into two compartments, corpora lutea of pseudopregnancy and remainder of ovary. Tissue samples were homogenized and prostaglandins extracted and determined by radioimmunoassay. During the mid-luteal and late-luteal phases, levels of PGs were significantly higher in the corpora lutea of pseudopregnancy than in the remainder of ovary. An increase of PGF2 alpha-content in the corpus luteum was registered with peak-levels of 53.9 +/- 8.5 (mean +/- SEM, N = 18) ng/g tissue wet weight at day 13 of pseudopregnancy. PGE-levels reached peak-values at day 11 of pseudopregnancy (271.6 +/- 28.4 ng/g w w, mean +/- SEM, N = 12). PGB-levels were below detection limits in all compartments for all ages studied. The present study demonstrates increased availability of PGF2 alpha in the corpus luteum during the luteolytic period, and points toward either increased luteal synthesis or luteal binding of PGF2 alpha during the luteolytic period.

Animals↗

Hormonal influence on utero-ovarian blood flow distribution in the mid-luteal pseudopregnant rat.

Uterine and ovarian blood flows and ovarian fractional perfusion were measured in adult rats anaesthetized with sodium pentobarbital i.p. on day 6 of pseudopregnancy, by using radioactive microspheres. Fifty i.u. human chorionic gonadotropin (hCG) was found to increase the fractional perfusion of the ovary, and this was at least partially accomplished at the expense of the uterine blood flow, since this was reduced. Noradrenaline (NA) infusion (2 nmol min-1) reduced ovarian as well as uterine blood flow acutely. After 20 min of NA infusion (2 nmol min-1), however, ovarian blood flow and fractional perfusion were increased, while no significant effect was seen for uterine blood flow. Antidiuretic hormone (ADH) in a 20-min infusion (1 nmol min-1) markedly reduced ovarian and uterine blood flows.

Animals↗

Studies of the luteinization process in the rat: development of catecholamine response on progesterone production during the peri-ovulatory period.

The present study was undertaken to investigate whether pre-ovulatory follicles have an adrenergic response in terms of progesterone production. Extirpated pre-ovulatory follicles obtained both before and after the endogenous gonadotropin surge and newly formed corpora lutea were obtained from the PMSG rat ovulatory model. Follicles and corpora lutea were incubated for 120 min in MEM with Earle's salt and 10 mM Hepes, 37 degrees C, pH 7.4 and 100% oxygen, with 30 microM noradrenaline or 10 micrograms ml-1 LH-B9). Pre-ovulatory follicles were barely stimulable by noradrenaline, while newly formed corpora lutea responded markedly. Luteinizing hormone (LH) levels significantly increased progesterone accumulation in all groups. In order to determine whether preovulatory follicles need intact surrounding tissue for an adrenergic response on progesterone production, pieces of ovaries containing pre-ovulatory follicles were incubated. No significant effect of noradrenaline or adrenaline was seen, while LH had a substantial effect. The results show that catecholamines acutely exert a selective effect on steroidogenesis in the ovary with a marked stimulatory effect on corpora lutea and a marginal effect on the pre-ovulatory follicle.

Animals↗

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↗

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↗

Blood flow changes and vascular appearance in preovulatory follicles and corpora lutea in immature, pregnant mare's serum gonadotropin-treated rats.

In the present study, synchronized follicular growth, ovulations, and luteogenesis were prematurely induced in 26-day-old immature rats by the s.c. injection of 4 IU of pregnant mare's serum gonadotropin (PMSG) at 2100 h. Relative blood flow of follicles/corpora lutea, fallopian tube, and uterus was measured with radioactive microspheres during the periovulatory period (Day 28, 1700 h-Day 31, 1300 h). Also, follicular/corpus luteal light microscopy and plasma progesterone were studied at the same intervals after PMSG injection. It was found that the relative follicular blood flow did not increase after the endogenous gonadotropin surge (Day 29, 0300-0500 h) and toward ovulation (Day 29, 1300-1500 h). During the same time period, light microscopy showed an interstitial edema and extravasation of erythrocytes appearing in the follicular wall near the time of ovulation. The relative blood flow reached its nadir in the young corpus luteum (21 h after ovulation) and increased thereafter (i.e., 48 h after ovulation). Plasma progesterone showed a preovulatory increase and then declined just prior to the ovulatory period. Between 24 and 48 h after ovulation, parallel increases in relative blood flow, morphological vascularization, morphological luteinization, and plasma progesterone levels were observed in the growing corpus luteum. These data indicate that a functional relationship between blood flow and steroid output may exist within the ovarian follicle and corpus luteum.

Animals↗

Influence of oxygen tension and substrates on basal and luteinizing hormone stimulated progesterone production and energy metabolism by isolated corpora lutea of adult pseudopregnant rats.

The effect of substrate reduction on in vitro progesterone production by isolated corpora lutea of pseudopregnant rats was studied. Pseudopregnancy was induced by mating adult females with vasectomized males. The rats were killed at different luteal ages and the corpora lutea of pseudopregnancy were identified, dissected free and incubated for 3 h. Six-day-old corpora lutea were incubated in the presence of different oxygen tensions as well as different glucose and amino acid concentrations and basal as well as luteinizing hormone (LH)-stimulated progesterone production was studied. When the oxygen tension was reduced, both basal and LH-stimulated progesterone production was decreased. At 6 and 0 kPa, the stimulatory effect of LH on progesterone production was abolished. Lowering the oxygen tension decreased the levels of adenosine-5'-triphosphate (ATP) in the tissue and increased lactic acid accumulation in the medium. Omitting both glucose and amino acids while maintaining oxygen tension at 100 kPa abolished the stimulatory effect of LH on progesterone production and decreased the levels of ATP. The present study shows that the corpus luteum in vitro is dependent on a high oxygen tension for maintenance of its progesterone production and LH responsiveness. It is suggested that the amount of ATP available is critical to the degree of LH response. Hypoxia increased luteal glycolysis, but this could only marginally compensate for a low oxygen tension.

Adenosine Triphosphate↗

Oxygen dependency of preovulatory follicles from pregnant mare serum gonadotropin-treated immature rats.

The present study was initiated to test to what extent preovulatory follicles are dependent on oxygen supply for maintaining their response to luteinizing hormone (LH). Female rats of the Sprague-Dawley strain were injected with 6 IU of pregnant mare serum gonadotropin (PMSG) on their 26th day of life. For in vitro experiments rats were killed 48-52 h after PMSG injection. Preovulatory follicles were dissected free, pre-incubated for 30 min and then incubated for 3 h without or with luteinizing hormone (LH, 1 microgram ml-1 medium) under different oxygen tensions in the gas phase (100, 13, 6 and 0 kPa). After incubation the accumulation of progesterone, cyclic-3',5'-adenosine monophosphate (cyclic AMP) and lactic acid were measured in the incubation media. Follicular adenosine-5'-triphosphate (ATP) content was measured in vivo (48-60 h after PMSG injection) immediately after isolation as well as after the incubation. Follicles isolated in vivo, during and after the ovulatory endogenous gonadotropin surge showed a depression in follicular ATP levels compared with levels before, suggesting that gonadotropins stimulate the follicle on the expense of ATP levels during the course of the preovulatory day. During a step-wise decrease of oxygen tension in vitro the preovulatory follicle maintained its response to LH as measured by progesterone and cyclic AMP accumulation. The preovulatory follicle could apparently compensate by increasing glycolysis, as measured by an increase in lactic acid accumulation. Tissue ATP levels were during these conditions maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

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↗

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↗

Comparison between pre- and postovulatory distributions of oestradiol and progesterone in the brain of the PMSG-treated rat.

The pre- and postovulatory levels of oestradiol and progesterone were measured in seven brain areas, peripheral fat, muscle tissue and blood plasma in 49 immature female rats which had been given an injection of 4 IU PMSG (Pregnant Mare Serum Gonadotropin) on the 25th day of life. We observed a uniform decline in oestradiol concentration in all the areas of the postovulatory rat. The highest mean concentrations of oestradiol pre- and postovulatory were found in the hypothalamus and the striatum (260 +/- 26, 110 +/- 11, 200 +/- 39 and 75 +/- 13 pg g-1, respectively). The levels of progesterone showed variable increases in all the areas postovulatory. The highest postovulatory concentration was found in the cerebral cortex (29 +/- 2.0 ng g-1) where the increase was six-fold greater than the increases in any of the other areas compared to preovulatory values. The hypothalamus contained high progesterone levels at both times (3.5 +/- 0.68 ng g-1 and 27 +/- 5.2 ng g-1) compared to other areas. We conclude that the female rat brain exhibits differences in the distribution of oestradiol and progesterone both pre- and postovulatory. Since the levels in different brain areas to a large extent varied independently we suggest different uptake mechanisms and/or different binding capacities in various regions of the rat brain.

Animals↗

A method for recording effects of anti-epileptic drugs on interictal discharge in the cat's cerebral cortex. Factors determining the distribution of external carotid artery infusions.

The method utilizes infusion via the external carotid (ECA), the internal maxillary arteries and their anastomoses to the cerebral circulation. It takes into account the ipsilateral distribution of the carotid blood supply. A regular interictal epileptiform spiking from foci on both hemispheres was provided by local application to the cortical surface of small pieces of filter paper soaked in sodium benzylpenicillin, 100,000 IE ml-1. The infused drug affects the ipsilateral foci, and the contralateral one functions as a simultaneous untreated control. The stability of the interictal frequency and the effect of non-oxygen carrying solvents are described. The effect of changes in blood pressure, temperature and PCO2 are considered as well as the coupling between activity in ipsi- and contralateral foci. Experiments with infused radioactive microspheres were performed to determine the strictness of the ipsilateral distribution and the conditions under which it was upheld. With mean arterial blood pressures between 70 mm Hg and 170 mm Hg and infusion speeds between 1.0 ml min-1 and 6.3 ml min-1 the distribution to the contralateral cerebral hemisphere was 0.3% (SD 0.2, SEM 0.1). Infusions of [125I]albumin were used to determine the blood flow in ECA. The flow varied between 20 ml min-1 and 68 ml min-1. The higher values were seen when the extracerebral shunting was high. Conditions influencing the dilution of the infusion and its distribution within the brain were investigated. Important factors were carotid and cerebral blood flow, arterial blood pressure, speed and duration of the infusion, recirculation and cerebral temperature. Arterial PCO2, pH and PO2 should be carefully controlled. Computer-supported treatment of interictal spike frequency and amplitude, as well as of circulatory and respiratory parameters, was utilized. The method was tested in experiments with infusions of 5 alpha-pregnanolone. It was shown that infusions, shorter than the estimated circulation time, reduced the interictal spike frequency and amplitude recorded from the ipsilateral foci without effects on the contralateral ones.

Animals↗

The human corpus luteum secretes 5 alpha-pregnane-3,20-dione.

A radioimmunoassay for 5 alpha-pregnane-3,20-dione (5 alpha-DHP) in plasma is described. The concentration of 5 alpha-DHP in peripheral plasma during the follicular phase of the menstrual cycle was of the same order of magnitude as that of progesterone (P). During the luteal phase, the plasma 5 alpha-DHP was 8-fold higher than in the follicular phase and about 1/3 of the P concentration. The concentration of 5 alpha-DHP in ovarian venous plasma draining an ovary containing the corpus luteum was 22-fold higher than the concentration in plasma from the contralateral ovarian vein. These results show that the corpus luteum secretes significant amounts of 5 alpha-DHP.

5-alpha-Dihydroprogesterone↗

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↗

Testosterone-induced decrement of prostatic vascular resistance in rats is reversed by estrogens.

The function and growth of the rat prostate are stimulated by androgens and inhibited by estrogens. To study the influence of these hormones on the prostatic blood flow, prostatic vascular resistance was measured in castrated adult rats, which were testosterone supplemented and treated with different estrogenic substances. Prostatic blood flow was measured using the microsphere technique. Testosterone supplementation for 8-9 days after castration resulted in decreased vascular resistance in both the ventral and dorsolateral prostates. In testosterone-supplemented rats, treatment for the same period of time with estradiol benzoate, ethinyl estradiol, and diethylstilbestrol induced increased vascular resistance in both the ventral and dorsolateral prostates. However, treatment with estromustine or estramustine did not change prostatic vascular resistance significantly. It was concluded that the testosterone-induced decrease of prostatic vascular resistance was reversed by estradiol, ethinyl estradiol, and diethylstilbestrol, possibly by a direct effect on the prostate.

Animals↗

Effects of human chorionic gonadotrophin, oestradiol and estromustine on testicular blood flow in hypophysectomized rats.

The effects of human chorionic gonadotrophin (hCG), eostradiol benzoate (E2) and estromustine (Eo) on testicular and prostatic blood flow and plasma levels of testosterone were studied in hypophysectomized rats. Daily injections of 5 IU hCG induced a significant increase in testicular blood flow when measured after 8-9 days treatment. This stimulatory effect was inhibited by concomitant injection of E2 (50 micrograms/day) but not by Eo. In contrast, the stimulatory effect of hCG on plasma levels of testosterone was inhibited by administration of E2 as well as by Eo. This inhibition was correlated with decreased blood flow to the prostate. The present study gives further support to the hypothesis the oestrogens have direct effects on the testis and prostate.

Animals↗