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Biomedical subjects

L Hamberger

Publications and source records attributed to L Hamberger.

At least 145 records · Page 8Linked to original sources

Hilus cells from human postmenopausal ovaries: gonadotrophin sensitivity, steroid and cyclic AMP production.

Strips of ovarian hilar tissue taken from 11 post-menopausal women were examined histologically and found to contain clusters of hilus cells in contiguity with non-myelinated nerve fibers. No other steroidogenically active structures were found. Specimens from these strips were incubated for 30 and 240 minutes in Krebs bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. The specimens produced measureable amounts of androstenedione, estradiol-17 beta and progesterone in vitro. The major steroid formed was androstenedione, and this pattern of steroidogenesis appeared similar to that of postmenopausal ovarian stroma. However, the amounts of steroids formed were considerably higher than in stromal tissue. This implies that the hilus cells possibly may be of greater importance, qualitatively, than the stroma cells for steroidogenesis in the postmenopausal ovary. Addition of hCG to the incubated specimens elicited increase in both cyclic AMP formation and steroid synthesis, especially of estradiol-17 beta, indicating a preserved responsiveness to gonadotrophin in hilus cells from postmenopasual ovaries.

Androstenedione↗

Copper and contractility of the human fallopian tube.

Muscle specimens were obtained from human oviducts during legal surgical sterilizations. Muscle strips (1 mm wide) were dissected from the circular and longitudinal muscle layers at the ampullary-isthmic junction, and contractile activity was recorded during short-term experiments in an organ bath. Administration of copper chloride induced a clear-cut excitatory response in both muscle layers. The response was, in many respects, similar to that evoked by low concentrations of prostaglandin F2 alpha (PGF2 alpha) but differed from the response induced by PGE2. Pretreatment of the tissue with indomethacin blocked the excitatory action of copper and frequently reversed the response into an inhibition of the contractile activity. After maximal stimulation of contractility by exogenous PGF2 alpha, copper was ineffective as a stimulant, whereas a maximal response elicited by copper could be further augmented by the addition of PGF2 alpha. The conclusion is that copper ions released from a copper intrauterine contraceptive device may increase contractility of the oviducts by an action on endogeneous synthesis of prostaglandins, predominantly of the F series. In addition, copper also seems to possess an inhibitory influence on motility of the oviducts, which becomes apparent only when the excitatory effect is blocked pharmacologically.

Adult↗

A new prostaglandin E2-gel for pretreatment of the cervix in nulliparous patients having a late first trimester termination of pregnancy.

A new PGE2-gel, based on a cross-linked starch powder, has been developed. This gel seems to have solved several of the pharmaceutical and practical problems connected with local administration of prostaglandins. In a three-center study 120 nulliparous patients were given 0.5 mg PGE2 in 2.2 ml gel intracervically prior to dilatation of the cervix and evacuation of the uterus in late first trimester. Considerable cervical dilatation was obtained within 15 h. The frequency of side effects, including pain and gastro-intestinal discomfort was low. The technique can be recommended for outpatients.

Abortion, Induced↗

Long-term clinical experience with the Cu-7-IUD. Evaluation of a prospective study.

In a prospective Swedish three-center study, totally 1446 women wearing a Cu-7-IUD were carefully followed for a minimum 2 years. Smaller subgroups have been followed for 4 years (n=278) or for even longer periods up to 8 years (n=48) with the same Cu-7-IUD in situ. Data are given concerning continuation rate, efficiency, expulsion, removals, pain, bleeding and risk for pelvic inflammatory disease. Prolonged use of the Cu-7-IUD beyond 2 years up to 4 years seems to be associated with fewer side effects and a lower incidence of accidental pregnancies than during the first 2 years of use. The computerized data confirm our earlier impression that the Cu-7-IUD provides a substantial efficacy and is associated with a relatively low rate of adverse effects.

Adolescent↗

The regulatory influence of prostaglandins on protein synthesis in the human non pregnant cervix.

Cervical connective tissue was obtained from non pregnant fertile women undergoing hysterectomy. Tissue specimens were mechanically chopped into 1 mm thick slices which were preincubated in Krebs-Ringer bicarbonate buffer containing PGE2 or PGF2 alpha (300 ng/ml). After 60 min the slices were transferred into fresh buffer with the corresponding PG-concentration and 3H-labelled proline or hydroxyproline. Following incubation (60 min) the protein bound radioactivity was determined and related either to the dry weight or to the protein content of each slice. The two methods used did not show any qualitative differences. The experiments showed that PG:s had a marked effect on protein synthesis in the cervical tissue. During the follicular phase incubation with both types of PG:s was followed by a decreased incorporation indicating decreased net synthesis of collagen while there was an increased incorporation and hence increased synthesis in the luteal phase. There was no significant influence on the distribution of the model amino acid 14C-AIB in the presence of PG:s neither in the follicular nor in the luteal phase. The present data point to an acute effect of PGE2 and PGF2 alpha on cervical collagen metabolism and indicate furthermore that the process is steroid hormone dependent. It is concluded that these substances may exert their effect by modulating the incorporation of amino acids into protein.

Amino Acids↗

Influence of 6-keto-PGF1 alpha on collagen synthesis in the human cervix during various phases of the menstrual cycle.

Uterine cervix tissue, obtained from nonpregnant fertile women undergoing hysterectomy, was mechanically chopped into 1 mm thick slices and incubated in Krebs-Ringer bicarbonate buffer containing 6-keto-PGF1 alpha (0.03-10 microgram/ml) and 3H-proline. After incubation of 30-120 min the incorporated radioactivity was determined and related to the protein content of each slice. 6-keto-PGF1 alpha had specific and significant effects on the incorporation of 3H-proline into cervical tissue. In the follicular phase of the cycle a decreased incorporation was registered, indicating a reduced net synthesis of protein. However, increased radiolabelling was observed in the luteal phase, reflecting an augmented protein synthesis. It is suggested that 6-keto-PGF1 alpha, the stable metabolite of prostacyclin (PGI2), has the ability to influence cervical protein metabolism and that this effect is steroid hormone dependent.

6-Ketoprostaglandin F1 alpha↗

Concentrations of copper in human secretions and weight of the copper wire during the 4 to 7 years after insertion of a Cu-IUD (intrauterine device).

The useful life span of the two most commonly used copper intrauterine devices (Cu-IUDs) (Gravigard and Cu-T) was investigated in a long-term study up to 90 months after insertion. Minor differences between the two types of devices were found that, however, probably do not contribute to a diverging contraceptive efficacy with time. To be able to ensure maximal contraceptive effect, the authors suggest on the basis of the present data that the time of use not exceed 5 to 6 years.

Adolescent↗

Acute effects of gonadotrophins and cyclic AMP on protein synthesis and progesterone production by isolated rat granulosa cells.

Amino acid uptake, protein synthesis and progesterone production were studied in rat granulosa cells, isolated from follicles of different stages of development. The amino acid uptake in granulosa cells from prepubertal rats was rapid with a distribution ratio above 1 within 10 min. No significant effects of gonadotrophins were observed on this parameter. The acute influence of exogenous LH and FSH or dibutyryl cyclic AMP (dbcAMP) on incorporation of 3H-leucine or 3H-phenylalanine was investigated as a measure of the rate of protein synthesis. In most experiments progesterone production was determined concomitantly. Both FSH (10 micrograms/ml or 100 micrograms/100 g b.wt.) and dbcAMP (a mM) stimulated (1.6--1.8 fold) the incorporation of leucine into granulosa cell proteins from prepubertal rats while LH was without effect. Progesterone production in these granulosa cells was very low and neither the gonadotrophins nor dbcAMP were stimulatory. Similarly designed experiments were performed on granulosa cells isolated from preovulatory rat follicles. It was then found that both FSH (10 micrograms/ml or 100 micrograms/199 g bst.) and dbcAMP (1 and 5 mM) as well as LH (10 micrograms/ml or 100 micrograms/100 g b.wt.) significantly (1.2--2 fold) stimulated protein synthesis. Furthermore, basal progesterone production was higher and was markedly stimulated (3--6 fold) by all three substances tested. The observations that the protein synthesis in immature granulosa cells is increased by exposure to FSH and dbcAMP while progesterone production in not, whereas both these parameters are stimulated with FSH, LH and dbcAMP in the preovulatory granulosa cells suggest that there might be certain differences in the nature of the proteins synthesized by immature and preovulatory granulosa cells.

Amino Acids↗

Influence of gonadotrophins on cAMP formation in theca cells isolated from pre-ovulatory rat follicles.

Pre-ovulatory follicles were obtained from immature PMSG treated rats at various times on the day of pro-oestrus. From these follicles the theca capsules were mechanically isolated and subsequently incubated in the presence or absence of LH and/or FSH. The accumulation of cyclic adenosine 3'5'-monophosphate (cAMP) in tissue plus medium was determined. In certain experiments the rats were injected with LH, FSH or saline 2 h prior to sacrifice. When the theca cells were isolated from rats sacrificed before the endogenous gonadotrophin surge, FSH added in vitro did not significantly stimulate cAMP formation, while LH had a small but significant stimulatory effect. When isolated 2-5 h after the endogenous gonadotrophin surge the theca cells responded with a marked increase in cAMP formation when exposed to LH in vitro, whereas FSH in vitro still had no stimulatory effect. Theca cells, isolated before the endogenous gonadotrophin surge, from rats pre-treated with a single ip injection of FSH 2 h prior to sacrifice, responded to a subsequent in vitro exposure to LH with a marked increase in cAMP levels. The results indicate that the FSH component of the endogenous gonadotrophin surge increases the sensitivity of the theca cells to LH - i.e. in vivo exposure to FSH seems to be essential for the development of responsiveness of the cAMP system to LH in the theca cells from pre-ovulatory rat follicles.

Animals↗

The ageing ovary.

Studies on the endocrine function of the ageing ovary are briefly reviewed. In the perimenopausal years, follicular function can become defective, leading to variable and often shortened cycle length and frequent anovulation. In the postmenopausal period the ovarian stromal cells continue to secrete variable amounts of steroid, mainly androgens. The endocrine activity of the postmenopausal ovary is generally too low to cause clinical symptoms. Occasional cases of hirsutism and even virilization have been reported in postmenopausal women with non-neoplastic lesions of the ovary.

Aging↗

Steroid production and responsiveness to gonadotropin in isolated stromal tissue of human postmenopausal ovaries.

Specimens from the ovarian cortical stroma of 15 postmenopausal women were examined histologically and were incubated for 4 hours in Krebs' bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. Specimens of normal postmenopausal stroma produced measurable amounts of androstenedione, estradiol, and progesterone in vitro. Specimens with stromal hyperplasia produced larger amounts of androstenedione and estradiol than those with normal stroma. Androstenedione was the predominant steroid produced in both groups. The nonnegligible formation of estradiol indicated an aromatizing capacity of the stromal tissue. The addition of hCG elicited a significant increase in cyclic AMP formation in specimens from ovaries with stromal hyperplasia, indicating a preserved responsiveness to gonadotropin in this type of ovaries.

Aged↗

A luteolytic effect of a prostaglandin F2 alpha analogue in non-pregnant women?

Four healthy non-pregnant volunteers with regular cycles were exposed to vaginal suppositories containing a PGF2 alpha analogue (ICI 81.008, 500-600 microgram) twice at 24-hour intervals in the early or mid-luteal phase. In comparison to serum progesterone levels of ovulatory control cycles, this treatment caused a significant decrease of serum progesterone combined with a shortening of the length of the luteal phase by 1.4 days. No gastrointestinal or other adverse effects were noticed during this treatment. Administration of ICI 81.008 in the follicular phase interfered neither with ovulation nor with the length or shape of the following luteal phase. Although limited, these data suggest a luteolytic effect of ICI 81.008 in women.

Adult↗

Contractile patterns of isolated oviductal smooth muscle under different hormonal conditions.

The isthmic portion of the human fallopian tube was excised during surgery and the ampullary-isthmic junction was identified. Muscle strips (1-mm wide) were dissected from the outer longitudinal and the inner circular layers at this region and used for isometric recordings of spontaneous contractile activity in organ bath experiments. It was found that the amplitude and the duration of individual contractions were similar during various phases of normal menstrual cycles, whereas the frequency of contractions was significantly increased during the periovulatory period in both circular and longitudinal muscle. During early pregnancy or treatment with combined oral contraceptives the motility pattern was similar to that observed in the late luteal phase, being characterized by a comparatively low contraction frequency. In the perimenopausal period, irregular patterns were frequently observed whereas preparations obtained from postmenopausal women exhibited a very weak activity with low amplitude and frequency of contractions. Similar activity was encountered in specimens from patients treated with androgens. It is concluded that endogenous estrogens stimulate human oviductal contractility while endogenous progesterone has a depressive action on tubal activity. Both effects occur with a certain delay and are prolonged for up to 3 days, i.e., the changes in the serum levels of ovarian steroids and the induced alterations of tubal contractility are out of phase.

Adult↗

Inhibition of LH-stimulated cyclic AMP formation in pre-ovulatory rat granulosa cells by follicular fluid.

Immature female rats were injected sc with a single dose of PMSG to induce growth and maturation of ovarian follicles. In the morning of prooestrus the rats were given a single ip injection of LH (10 micrograms/rat) or 0.154 M NaCl, 2 h prior to sacrifice. Granulosa cells were isolated fro the pre-ovulatory follicles and incubated in Krebs bicarbonate buffer, for 1 h with or without in vitro addition of various test substances. Following incubation the amounts of cAMP in tissue plus medium were determined. It was found that the isolated granulose cells exposed to LH in vivo responded to the addition of LH in vitro with a production of high amounts of cAMP, i.e. these cells were not refractory to LH stimulation and in fact responded better than granulosa cells isolated from ovaries not exposed to LH in vivo. The addition to the incubation medium of follicular fluid (FFl) obtained from pre-ovulatory follicles decreased the effect of LH in vitro when added at a final concentration of 1% and completely abolished it at a concentration of 3%. Removal of steroids from the FFl did not influence the inhibitory effect and the addition of a phosphodiesterase inhibitor (IBMX) in vitro did not alter the results in principle. These results point to the existence of a factor in the FFl which interacts with the sensitivity of the isolated pre-ovulatory granulosa cells to repeated exposures to LH. Characterization of this factor is subject to further investigations.

Animals↗

Steroid production in vitro of a hilus cell tumor of the human ovary.

A 69-year-old heavily virilized woman with an androgen-producing tumor of the right ovary is described. After tumor removal, plasma testosterone levels fell from 5 to less than 0.6 ng/ml. Serum gonadotropins were low prior to surgery and rose to high levels postoperatively. Histologic examination of the right ovary revealed a hilus cell tumor. Incubation of small specimens of tumor tissue for 2 hours in oxygenated Krebs bicarbonate buffer containing glucose and bovine serum albumin yielded a release of predominantly testosterone and androstenedione into the medium. Human chorionic gonadotropin (hCG) added to the medium had no effect on steroid release. Incubation of tumor tissue in vitro may provide a useful functional adjuvant to the morphologic characterization of hormone-producing ovarian tumors. Such combined studies may increase our knowledge of the much-debated histogenesis of these tumors.

Aged↗