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Biomedical subjects

L Hamberger

Publications and source records attributed to L Hamberger.

At least 127 records · Page 7Linked to original sources

Interaction between catecholamines and prostaglandin F2 alpha in human luteolysis.

From each of 14 women undergoing laparotomy at different stages of the luteal phase of the cycle, the corpus luteum (CL) was excised, cut into pieces and incubated for 120 min. Incubations were performed in the absence and presence of hCG and prostaglandin F2 alpha (PGF2 alpha). In addition, noradrenaline (NA) was added to the incubation medium of newly formed CL, and the adrenergic blocker propranolol to incubated specimens of mid-luteal phase CL. After incubation the tissue levels of protein and cyclic AMP (cAMP) and the media concentrations of progesterone (P) were determined. In young CL, PGF2 alpha did not interfere with the stimulatory effect of hCG on neither cAMP nor P formation, while in CL of the mid-luteal phase PGF2 alpha significantly counteracted the stimulatory effect of hCG on these two parameters. In the presence of propranolol, however, this antigonadotrophic effect of PGF2 alpha in vitro was abolished. Furthermore, when NA was added to specimens of young CL, PGF2 alpha significantly counteracted the stimulatory effect of hCG on both cAMP and P formation. These in vitro data show that endogenous catecholamines may regulate the antigonadotrophic, 'luteolytic' effect of PGF2 alpha in human CL.

Chorionic Gonadotropin↗

Collection of human oocytes by the use of sonography.

A technique for ultrasonically guided percutaneous oocyte aspiration was developed utilizing standard real-time, linear-array ultrasound equipment. Forty-four patients attending our in vitro fertilization and embryo transfer (IVF-ET) program were included in this study. In 38 patients, follicular puncture was performed under general anesthesia and in 6 cases performed under local anesthesia. Fifty-two follicles with a mean diameter greater than or equal to 18 mm were punctured, and 40 mature oocytes were recovered corresponding to a success rate of 77% per follicle. Six of the punctured follicles were considered cystic when the aspirated granulosa cells were examined microscopically and, if these were excluded, the corrected recovery rate was 87% per follicle. In two patients, ovulation had occurred at the time for oocyte collection. In one of these patients, a mature oocyte was, however, recovered from the pouch of Douglas by the use of sonography. On the basis of these results, ultrasonically guided puncture of follicles for collection of human oocytes in our IVF-ET program seems suitable for use in all cases where laparoscopy is presently used and, moreover, in cases with severe adhesions, where laparoscopy may fail.

Embryo Transfer↗

Inhibition of progesterone secretion in cultured human granulosa cells by a low molecular weight fraction of human follicular fluid.

Previous studies demonstrated that a low molecular weight peptide fraction (G10-3) from human follicular fluid (FFl) could inhibit steroidogenesis by rat granulosa cells in vitro. In the present study this FFl fraction was tested upon human granulosa cells. The G10-3 fraction (less than 1000 mol wt) was obtained by sequential gel filtration on Sephadex G50 and G10 of a steroid-free extract of a pool of human FFl collected from various-sized follicles at different stages of the menstrual cycle. Human granulosa cells were obtained from large, healthy follicles in the mid- to late follicular phase of eight patients, and cultured for 4-6 days in the absence or presence of G10-3. In all cases G10-3 produced a dose-dependent inhibition of basal progesterone secretion and, when tested, also of FSH-stimulated progesterone secretion. Inhibition of progesterone secretion appeared to be greater in cells obtained from less mature follicles as compared to cells obtained from follicles that were periovulatory. The results suggest the presence of a low molecular weight luteinizing inhibitor in human FFl.

Body Fluids↗

Aspects concerning the role of prostaglandins for ovarian function.

The present review briefly summarizes the current view of the mechanisms whereby prostaglandins (PGs) may act to modulate ovarian function. Particular concern is devoted to the aspects of ovarian function which are under current investigation by the authors, namely follicular maturation and rupture, granulosa cell and oocyte maturation, and the formation and maintenance as well as the regression of the corpus luteum (CL). PGs are formed in the granulosa cells of the preovulatory follicle in response to gonadotropin action and are at their highest levels around the time of ovulation. PGs are believed to be obligatory for follicular rupture, but their mechanism of action is still unknown. In the process of oocyte maturation PGs can mimic the stimulatory effects induced by LH or hCG, but are probably not obligate mediators of these effects. The importance of PGs for CL formation and maintenance is so far unsettled, and PGs may be regarded more as modulators than as inducers for these processes. The most well-documented effect of PGs is the induction of CL regression. Evidence is presented that PGs may have this effect also in the human.

Alprostadil↗

Experimental studies on the influence of prostaglandins on the connective tissue of the human cervix uteri.

The influence of prostaglandins (PGs) on the synthesis of collagen and proteoglycans in the human cervix was estimated by incubation in vitro of cervical biopsy samples in the presence of tritiated amino acids and glucosamine after addition of PGE2, PGF2 alpha and 6-keto-PGF1 alpha. In the follicular phase of the menstrual cycle PGs increased the labelling with [3H] glucosamine but reduced the labelling with [3H] hydroxyproline, [3H] proline and [3H] glycine. Conditions were reversed in the luteal phase. The stable metabolite of PGI2, 6-keto-PGF1 alpha, had an effect similar to that of the classical PGs. In the early period of the first trimester the pattern of PG effects was the same as in the luteal phase, i.e. the labelling with [3H] proline was increased and the incorporation of [3H] glucosamine was reduced after treatment with PG. At the end of the first trimester, PG affected the radiolabelling in an inverse way. It is concluded that PGs are involved in the control of the biosynthetic activity of the cervical connective tissue. PGs may play a role of modulators, reinforcing or accelerating the current biosynthetic activity, and directed mainly by hormonal, neuronal and other factors.

6-Ketoprostaglandin F1 alpha↗

Interaction between PGs and catecholamines on cervical collagen synthesis.

Specimens from the upper part of the cervix were excised and chopped into 1 mm thick slices. These were incubated in buffer containing [3H] proline fortified with PGE2 and/or NA and the incorporation into total protein was measured after various incubation periods. In certain experiments the slices were preincubated with reserpine to deplete the tissue stores of catecholamines. Both PGE2 and NA were able to influence the incorporation of [3H] proline in such a way that the stimulatory effect of PGE2 was counteracted by reserpine in the luteal phase of the cycle, while NA-stimulated incorporation of [3H] proline was inhibited by PGE2 in the late follicular phase. Both clinical and experimental studies have shown that PGs per se interfere with the biophysical and biochemical properties of the cervix. The present results indicate that there also exists an interaction between PGs and catecholamines.

Cervix Uteri↗

Second-trimester abortion by extra-amniotic instillation of Rivanol combined with intravenous administration of oxytocin or prostaglandin F2 alpha.

Induction of second-trimester abortion was studied by administration of the acridine derivative Rivanol in combination with an i.v. drip infusion of oxytocin or prostaglandin F2 alpha (PG2 alpha), alone or in combination. It was found that an early onset of the i.v. infusion was of major importance for the outcome. Administration of oxytocin in immediate connection with the Rivanol instillation proved more favorable than administration of PGF2 alpha) or a combined oxytocin PGF2 alpha drip, taking into consideration the induction-abortion time as related to the side effects. A lag phase between the instillation of Rivanol and the start of i.v. infusion such as has earlier been frequently recommended seemed to be of no specific advantage, but caused both a prolonged induction-abortion time and an increased incidence of infection.

Abortion, Induced↗

Influence of human chorionic gonadotropin in vivo on steroid formation and gonadotropin responsiveness of isolated human preovulatory follicular cells.

Granulosa and thecal cells of preovulatory follicles taken from 12 women were isolated and incubated separately for 2 hours in the presence and absence of human chorionic gonadotropin (hCG). To six of these women, an ovulatory dose of hCG (9000 IU) had been given 24 to 30 hours before excision of the follicle. Following incubation, cellular cyclic adenosine 3':5' monophosphate (cAMP) levels and the medium content of progesterone (P), androstenedione (A), and 17 beta-estradiol (E2) were determined. All follicles appeared healthy and well developed, and the oocytes recovered were morphologically normal and mature. Exposure to hCG in vivo caused a shift in steroidogenesis from A toward P formation in isolated thecal cells and a marked increase in the P production by the granulosa cells of the preovulatory follicles. Furthermore, the thecal cells, but not the granulosa cells, developed refractoriness to further stimulation with hCG in vitro.

Adult↗

PGI2 may play a role in the pathophysiology of dysmenorrhea.

Small longitudinally or helically cut strips from the ascending branch of the uterine artery were mounted in organ chambers for isometric recording of contractile activity. PGI2(3-300 ng/ml) caused a concentration-dependent relaxation of spontaneously active preparations, whereas no inhibitory effect could be observed on non-active strips. Furthermore, the compound counteracted the stimulatory effects of PGE2, PGF2 alpha, and NA, but not that of transmural nerve stimulation. The effect of PGI2 could be of interest in that the compound may balance the action of vasoconstricting agents. A disturbance of this balance may be a hitherto unrecognized contributing pathophysiological mechanism in the development of dysmenorrhea.

Arteries↗

Prostaglandins and oviductal function.

This review presents evidence of a specific involvement of PGs in the function of the human Fallopian tube. A role of PGE and PGF in ovum transport seems plausible, but data from human studies are still fragmentary. High estrogen levels in tissue at ovulation may cause 'tubal lock' by increasing the activity of the isthmic musculature. This effect might be exerted by an estrogen-dependent increase in the formation of PGF as well as by increased sensitivity to PGF. The elevation of progesterone levels in the early luteal phase would counteract the effect of estrogens by instead favoring E prostaglandins. PGE seems to relax the isthmic muscle, allowing the entry of the fertilized ovum into the uterine cavity.

Alprostadil↗

Collagen synthesis inhibition by PGE2 within the human follicular wall--one possible mechanism underlying ovulation.

Follicular wall specimens were taken from various parts of human preovulatory follicles as well as from less developed follicles. The tunica albuginea was isolated and incubated for 2 h in Krebs Ringer bicarbonate buffer containing 3H-proline in the presence or absence of PGE2 (0.1 microgram/ml). Following incubation the incorporated radioactivity was determined and related to the protein content of each strip. PGE2 had a specific effect on the incorporation of 3H-proline into protein in the follicular wall. In the apical part of the preovulatory follicle a significantly decreased incorporation was registered, indicating a reduced net synthesis of collagen. However, PGE2 was without effect on specimens derived from the non-apical parts of the preovulatory follicles as well as from the less developed follicles. It is suggested that the registered biochemical changes induced by PGE2 are of importance for the process of human ovulation.

Adult↗

Recruitment of an ovulatory follicle in the human following follicle-ectomy and luteectomy.

The study was undertaken to explore the time required for the selection and ovulation of a dominant follicle after interference with the normal menstrual cycle of fertile women. At routine laparotomy (sterilization) a leading follicle or a fresh corpus luteum was excised, and the day of the next ovulation was estimated by monitoring of serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and 17 beta-estradiol and by registration of the growth of the follicles through ultrasonic scanning. The results are in accordance with earlier observations in the rhesus monkey demonstrating that the recruitment and selection of an ovulation-competent follicle takes 12 to 14 days in the primate. Since this time is close to the length of the normal follicular phase and approximately the same after follicle-ectomy and luteectomy, the results suggest an importance of local factors in regulating follicle recruitment.

Adult↗

Countercurrent exchange of progesterone and antipyrine between human utero-ovarian vessels, and of antipyrine between the femoral vessels in the cat.

The utero-ovarian vein and ovarian artery in surgical specimens were cannulated and perfused in a countercurrent manner with isotonic, buffered solutions, fortified on the venous side with progesterone or radiolabelled methylantipyrine. Both substances were gradually transferred from the vein into the artery in the majority of the experiments while albumin was not exchanged. The results point to the existence of a countercurrent exchange mechanism in the human ovarian pedicle. Hardly detectable amounts of methylantipyrine were transferred from femoral vein to artery in the cat.

Animals↗

Steroid and adenosine 3',5'-monophosphate formation in granulosa and thecal cells from human preovulatory follicles in response to human chorionic gonadotropin.

Granulosa and thecal cells from the preovulatory follicles of 14 women were mechanically isolated and separately incubated for short term periods (0.5-4 h) in the presence and absence of hCG. After incubation, tissue cAMP levels and medium progesterone content of (P), androstenedione (A), and 17 beta-estradiol (E2) were determined. All follicles appeared healthy and mature, as judged by their number of granulosa cells, histological examination of the oocytes, athe steroid levels in antral fluid, as well as the appearance of the oocyte-cumulus complexes. Under basal conditions, both granulosa and thecal cells had the capacity to synthesize all of the steroids measured. The predominant steroid formed by the granulosa cells was P, while the thecal cells formed A as the major steroid. Both cell types produced considerable amounts of E2. The addition of hCG in various concentrations gave rise to concentration-dependent increase in cAMP formation in both cell types. Furthermore, hCG caused a statistically significant increase in the formation of P and A by the thecal cells, while steroid formation by the granulosa cells was not significantly altered. With higher concentrations of hCG, however, there was a tendency toward a stimulation of P synthesis in the granulosa cells from most of the follicles tested. It is concluded that in preovulatory follicles of human origin, follicular steroidogenesis is not rigidly compartmentalized between the two cell types. Furthermore, both granulosa and thecal cells are sensitive to stimulation with hCG in this type of follicle.

Adult↗

Progesterone and adenosine 3',5'-monophosphate formation by isolated human corpora lutea of different ages: influences of human chorionic gonadotropin and prostaglandins.

From each of 24 women undergoing minilaparotomy at various stages of the luteal phase of the cycle, the corpus luteum (CL) was excised in toto, decapsulated, cut into pieces, and incubated for short time periods (5--120 min). Incubations were carried out in the absence and presence of hCG, prostaglandin F2 alpha (PGF2 alpha) and PGE2, both alone and in combination. Dating of the CL was done meticulously using several parameters. After incubation, the tissue levels of cAMP and the media concentrations of progesterone (P) were determined. The basal P production in vitro was highest in CL of the midluteal phase. hCG stimulated cAMP formation in CL of all ages, with the highest levels of cAMP being produced in CL of the midluteal phase. PGE2 was found to increase cAMP formation and potentiate the hCG effect in young CL, but not in CL of the midluteal phase. PGF2 alpha, alone or in combination with hCG, had no effect on cAMP or P formation in either young or old CL, while in CL of the midluteal phase, PGF2 alpha significantly counteracted the stimulatory effect of hCG on both cAMP and P formation. These in vitro data show that PGF2 alpha is capable of inducing functional luteolysis in humans.

Adult↗