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Biomedical subjects

H R Lindner

Publications and source records attributed to H R Lindner.

At least 55 records · Page 3Linked to original sources
PubMed1979

Effect of modulators of cytoskeletal function on desensitization and recovery of PGE2-responsive ovarian adenylate cyclase.

Exposure of cultured Graafian follicles to PGE2 for 20 h resulted in a loss of the cyclic AMP response to fresh hormone. This desensitization was prevented by addition to the medium of D2O (25--50%) or Li+ (0.6--6 mM), agents believed to stabilize microtubules, as well as by phalloidin (1.0--10 microM), believed to stabilize the polymerized state of actin, in a dose-dependent manner. The spontaneous recovery of responsiveness to PGE2 upon incubation of refractory follicles for 6 h in hormone-free medium was prevented by addition to the medium of cytochalasin B (CB; 3 microgram/ml) or of the actin-binding myosin subfragment HMM S-1 (80 microgram/ml) or of anti-actin serum; viz. by agents likely to interfere with microfilament function. D2O (50%) caused morphological damage to the inner layer of the membrana granulosa and severe depression of protein synthesis. The other drugs used (phalloidin, LiCl and cytochalasin B) had no such effects. Resensitization of refractory follicles was also prevented by cycloheximide (10 micrograms/ml) and by actinomycin D (10 micrograms/ml). It is speculated that the recovery process may involve the insertion of a newly synthesized protein, such as PG-receptor, into the membrane by a mechanism dependent on microfilament action. These findings provide suggestive evidence for the hypothesis that cytoskeletal elements associated with the cell membrane take part in the modulation of the adenylate cyclase response to hormones.

Actins↗
PubMed1978

Effect of flufenamic acid on uterine contractions and plasma levels of 15-keto-13,14-dihydroprostaglandin F2alpha in preterm labor.

Flufenamic acid (FA), an inhibitor of the synthesis and action of prostaglandins, was administered to 18 women with preterm labor during the 28th to 36th week of gestation. In 15 patients delivery postponed, the mean admission/delivery interval being 21.5 days. 2 patients with cervical dilatation of 4 cm delivered within 48 h despite medication. The peripheral plasma levels of 15-keto-13,14-dihydroprostaglandin F2alpha (KH2 PG2alpha) was high on admission (216 +/- i4 pg/ml, mean +/- SEM), declined by 50% within 2 h of instituting treatment and remained near the normal level seen in 13 controlled women after the 24th hour.

Adult↗
PubMed1977

Localization of actin and myosin in the rat oocyte and follicular wall by immunofluorescence.

The distribution of actin and myosin in the rat ovary at different stages of postnatal development was studied by examination of cryostat sections treated with antibodies to chicken smooth muscle (gizzard) myosin or to chicken (pectoral muscle) actin and subsequently with fluoresceinated goat anti-rabbit gamma-globulins. Staining with either antiserum revealed several layers of intensely fluorescent elongated cells within the theca externa, forming a coherent band around the larger Graafian follicles. In smaller follicles, this band of fluorescent cells was incomplete, and ovaries of immature (6-day-old) rats were devoid of strongly fluorescent cells. Corpora lutea contained only scattered fluorescent cells at their circumference. Sections of mature ovaries incubated with antibodies raised against striated (pigeon pectoral) muscle myosin generated no significant fluorescence. Large oocytes stained with either anti-actin or anti-smooth muscle myosin showed a thin fluorescent band just beneath the zona pellucida, suggesting that actin and myosin are associated with the oolemma. The distribution of the two antigens in serial sections of follicles coincided, suggesting that the same cells contained both actin and myosin. It is suggested that follicular growth and maturation is attended by the development of a smooth muscle layer in the theca and that contraction of this layer in response to catecholamines and/or prostaglandins may play a role in the extrusion of the oocyte. The role of contractile elements in the oocyte remains to be elucidated.

Actins↗
PubMed1977

Stimulation by cyclic nucleotides of prostaglandin E production in isolated graafian follicles.

Rat Graafian follicles isolated intact responded to 8-Br-cyclic AMP and 8-Br-cyclic GMP with increased prostaglandin E (PGE) production during a 6 h incubation. By contrast, 8-Br-cyclic IMP, 8-Br-5' AMP and 8-Br-5' GMP were inactive in this respect. The effect of 8-Br-cyclic AMP and 8-Br-cyclic GMP was noted only after a lag period of about 4 h. Choleragen, LH, and the phosphodiesterase inhibitor (3-isobutyl-l-methyl-xanthine; IBMX) also stimulated PGE production. Actinomycin D and cycloheximide given simultaneously with 8-Br-cyclic AMP or LH prevented the stimulatory effect of these agents. Concomitant addition of arachidonic acid did not overcome the effect of these inhibitors. Administration of hCG in vivo or incubation with LH in vitro did not elevate endogenous ovarian free arachidonate, while PGE production was enhanced. Dexamethasone prevented this stimulatory effect of hCG. Collectively, the results suggest that stimulation of ovarian PGE production by cyclic nucleotides and LH is dependent on de novo synthesis of one or more components of the PG synthetase system rather than on substrate availability. Cyclic nucleotides may mediate the stimulatory effect of gonadotropins on PGE production.

Adenosine Monophosphate↗
PubMed1977

Suppression of 20 alpha-hydroxysteroid dehydrogenase activity in cultured rat luteal cells by prolactin.

20alpha-Hydroxysteroid dehydrogenase (20 alpha-SDH) activity increases in the cycling corpus luteum of the rat, beginning at 14.00 h on the day of diestrus, but remains low in corpora lutea of pregnancy throughout the first 19 days of gestation. When cells derived from 7-day-old corpora lutea of pregnant rats were cultured for 7 or 12 days, there was a spontaneous rise in 20 alpha-SDH activity from an initial value of 0.44 +/- 0.27 to 4.1 +/- 0.7 units/mg supernatant protein. Addition of LH (NIH-S-18; 2.0 mug/ml) or prostaglandin F2alpha (2.8 X 10(-5) M) to the medium from day 4 to the end of incubation period caused a slight but significant reduction in 20 alpha-SDH activity (20%, P less than 0.05). Supplementation of the medium with ovine prolactin (HIH-P-S11; 10.0 mug/ml) from the time of seeding or from the 2nd to 4th day of culture reduced the activity of 20 alpha-SDH measured on day 12 by 61% (P less than 0.001). This finding suggests that the suppression of 20 alpha-SDH by prolactin, hitherto demonstrated only in vivo results from a direct action of the hormone on the luteal cell.

Animals↗
PubMed1977

Acute effect of delta1-tetrahydrocannabinol on the hypothalamo-pituitary-ovarian axis in the rat.

Administration of delta1-tetrahydrocannabinol (delta1-THC), the principal psychoactive ingredient of cannabis, to proestrous rats (2 mg/rat, i.p., between 12.00 and 16.00 h) suppressed the proestrous rise in the plasma levels of LH, FSH and prolactin (Prl) and caused a 24 h delay in ovulation. Furthermore, the increased accumulation of prostaglandins of the E-type (PGE) in the ovaries, normally seen on the evening of proestrus, was prevented. Earlier (08.00-10.30 h) or later (18.00 h) administration of the drug on the day of proestrus was only partially effective in inhibiting ovulation. The suppressive effects of delta1-THC on ovulation and gonadotropin secretion were prevented by administration of gonadetropin releasing hormone (GnRH, 0.2 microgram/rat) 1 h after the drug, indicating that the central action of delta1-THC was exerted on the hypothalamus and not on the pituitary gland. Administration of ovine luteinizing hormore (oLH, 2.5 microgram/rat at 16.30 h on the day of proestrus restored ovulation and ovarian PGE accumulation in Nembutal-treated rats, but not in delta1-THC-treated rats; higher doses of oLH (5-10 microgram/rat) reversed the action of delta1-THC on these two parameters.

Animals↗
PubMed1977

Endocrine and reproductive repercussions of immunization against progesterone and oestradiol in female rats.

Mature female rats were immunized with BSA-conjugates of oestradiol-17beta-6-carboxymethyloxime or progesterone-11-hymisuccinate. Sera tested two months later at 1/2000 dilution bound 63.3% +/- 3.1 SEM and 21.2% +/- 2.3 of the homologous tritiated hormone (10 pg),--oestradiol-17beta(Oe2) and progesterone (P), respectively. Rats immunized against Oe2 had a significantly longer oestrous cycle (8.2 days vs. 4.5 days in BSA-immunized rats), with a prolonged leukocytic phase. The cycle of rats immunized against P was also prolonged (10.5 days), but in this group the cornified smear phase was abnormally extended. The luteinizing hormone (LH) normally observed on the afternoon of pro-oestrus failed to occur in the rats immunized against Oe2 and in 70% of rats immunized against P. The latter animals, however, showed sporadic LH discharges during periods of persistent cornification. Immunization against P resulted in elevated total (free plus bound) plasma P levels; immunization against Oe2 prevented the pro-oestrous rise in plasma P. Mating of rats immunized against Oe2 resulated in normal pregnanices, while none of the rats immunized against P delivered.

Animals↗
PubMed1977

Differentiation of decidual cells in cultures of rat endometrium.

Endometrial scrapings were collected from rat uteri at various times (0-4 days) after induction of a decidual reaction by i.p. injection of pyrathiazine hydrochloride (20 mg/animal) on the 5th day after a sterile mating. The tissue was dissociated by treatment with trypsin and the cells were cultured as monolayers. The differentiation of decidual cells was followed in these cultures. Two morphologically distinct cell populations were recognized: (i) dispersed spindle-shaped or stellate cells, and (ii) colonies of closely packed polygonal cells, first apparent after 48 h in culture. During culture, [3H] thymidine was incorporated into the nuclei of both cell types, as indicated by autoradiography. There was an increase in the number of cells in the colonies as culture progressed; most mitotic figures and the highest % of labelled nuclei were located within the colonies. Bi- and multinucleated cells, which are a characteristic feature of decidual tissue in vivo, appeared in the colonies on the 3rd day of culture and constituted about 60% of the colony population after 4-5 days. The dispersed cells showed a doubling in nuclear area during 4 dyas in culture, suggesting the formation of polyploid cells; such cells are prominent in fully differentiated decidual cells in vivo. The content of prostaglandin E in the cultured cell, determined by radioimmunoassay, was about 15-fold higher than that in rat embryo fibroblast cultures grown under similar conditions, and was comparable to the level of prostaglandins found in decidual cells in vivo.

Animals↗
PubMed1977

Changes in steroid concentration in the ovaries of immature rats treated with pregnant mare serum gonadotrophin and human chorionic gonadotrophin.

The concentrations of testosterone, progesterone and 20alpha-hydroxypregn-4-en-3-one (20alpha-OHP) were measured in the ovaries of immature rats in which ovulation was induced by treatment with pregnant mare serum gonadotrophin (PMSG) and, 48 h later, with human chorionic gonadotrophin (HCG). The concentration of testosterone in the tissue increased significantly 48 h after treatment with PMSG, reached a peak 4 h after the administration of HCG and declined to the basal level 4 h later. Increases in the levels of progesterone and 20alpha-OHP were observed 4 h after the administration of HCG. Whereas the level of 20alpha-OHP continued to rise during the subsequent 30 h, progesterone levels declined near the presumed time of ovulation (12 h after administration of HCG). It is concluded that 20alpha-hydroxysteroid dehydrogenase activity is present in the immature rat ovary before ovulation and that an increase in the production of testosterone in the ovaries of rats treated with PMSG and HCG precedes increased production of progesterone and 20alpha-OHP in these ovaries.

20-alpha-Dihydroprogesterone↗