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Biomedical subjects

H R Lindner

Publications and source records attributed to H R Lindner.

At least 19 recordsLinked to original sources

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

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

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

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