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Biomedical subjects

A Nimrod

Publications and source records attributed to A Nimrod.

At least 37 records · Page 2Linked to original sources
PubMed1986

Stimulation of creatine kinase activity in rat organs by human growth hormone in vivo and in vitro.

Intraperitoneal injection of human GH (hGH) (4 micrograms/g BW) into 21-day-old rats causes, 24 h later, an increase in creatine kinase (CK) specific activity in kidney (1.7-fold), liver (1.6-fold), and in epiphyseal cartilage (1.8-fold). Similar stimulation was obtained when tissue explants were incubated for 24 h with hGH (1 microgram/ml); CK activity rose 1.8-fold in kidney, 1.9-fold in the liver, and 2.6-fold in epiphyseal cartilage. Highly significant stimulation of CK specific activity was obtained in these same organs in hypophysectomized rats. The increase in CK specific activity in the kidney, to some extent in the liver, but not in the epiphyseal cartilage, was also obtained on in vivo treatment with either human placental lactogen or ovine PRL. Stimulation of CK in these three organs by hGH is followed by a parallel increase in DNA synthesis. Dexamethasone, which was also found to increase CK activity in rat kidney and liver, did not affect the increase of CK by hGH in the kidney, stimulated the effect of hGH in the liver, and partially inhibited the effect of hGH in the epiphyseal cartilage. Diethylaminoethyl cellulose chromatography revealed that the basal and induced activity of CK in all cases was due to the brain type isozyme. On the basis of this evidence for a direct effect of hGH on CK brain type activity, we suggest that its stimulation is potentially a convenient and sensitive assay for biological activity of GH.

Animals↗
PubMed1985

Characterization of the maturational changes induced by a GnRH analogue in the rat ovarian follicle.

The GnRH analogue [D-Ser(t-Bu)6]des-Gly10-GnRH-N-ethylamide (GnRHa, 2 micrograms/rat) or hCG (4 i.u./rat) was administered to hypophysectomized, PMSG-primed immature female rats. Oocyte maturation was initially detected by 2 h after GnRHa administration but the response to hCG was observed only after 4 h. Initiation of GnRHa-induced ovulation also preceded the response to hCG by 2 h. Maximal response to both these hormones was obtained at 10 and 14 h after hormone administration for oocyte maturation and ovulation respectively. The number of oocytes ovulated after GnRHa was significantly lower than that with hCG (29 +/- 4 and 50 +/- 7 per rat respectively; P less than 0.05). Expansion of the cumulus mass and secretion of mucoid material, which are characteristic responses to LH, were also observed after GnRHa administration. However, while the action of 5 micrograms ovine LH/ml on the cumulus cells was mediated by cAMP, no accumulation of the nucleotide could be detected in follicles exposed to GnRHa (10(-7) M). We conclude that even though GnRHa and LH/hCG seem to elicit similar responses in the ovarian follicle they differ in their kinetics, their efficiency and the mediator of their action.

Animals↗
PubMed1984

The suppressive effect of delta-1-tetrahydrocannabinol on the steroidogenic activity of rat granulosa cells in culture.

In previous study the major psychoactive ingredient of marihuana (delta 1-THC) has been shown to inhibit ovarian prostaglandin synthesis when administered to normally cycling rats in the early afternoon of proestrus. These results suggested a direct suppressive effect of the drug on the ovary. The purpose of this study was to evaluate the effect of delta 1-THC on steroidogenesis in granulosa cells (GC) in vitro. Incubation of GC with delta 1-THC (10-50 microM) effectively inhibited LH-stimulatable progestin production. This suppressive effect was not abolished by washing the cells after 24 h of culture in the presence of delta 1-THC, indicating the irreversible nature of the blocking effect of delta 1-THC. By contrast, estradiol production following incubation of GC with testosterone (1 microgram/ml) was not inhibited by similar concentrations of delta 1-THC, thus suggesting that delta 1-THC does not inhibit aromatase activity in GC. In addition, delta 1-THC was shown to inhibit cAMP production as well as 125I-hCG binding capacity to GC. Administration of 8-Br-cAMP did not abolish the delta 1-THC-induced block, suggesting that the drug probably acts distal to the cAMP site of action.

20-alpha-Dihydroprogesterone↗
PubMed1983

Role of FSH and oestradiol-17 beta in the development of meiotic competence in rat oocytes.

The ability of rat oocytes to resume meiotic maturation upon isolation ("meiotic competence") was shown to be abolished by hypophysectomy on day 15 post partum (p.p.). FSH (NIAMD-rat FSH-B-1; 10-20 micrograms/day), but not LH (NIAMD-oLH-21; 2-20 micrograms/day) was able to induce meiotic competence in rats hypophysectomixed on day 15 pp. Implantation of a capsule of oestradiol-17 beta, but not of progesterone or androstenedione, partially restored meiotic competence in hypophysectomized rats within 24 h of treatment. When inhibitors of steroidogenesis (aminoglutethimide, 17 beta-formamidoandrost-4-en-3-one, 1,4,6-androstatriene-3,17-dione or 4-hydroxy-4-androstene-3,17 dione) were coadministered with FSH they inhibited its effect on the development of meiotic competence. Furthermore, when oestradiol-17 beta was administered together with these inhibitors of steroidogenesis, the effect of FSH on the development of meiotic competence was not disturbed. These results strongly suggest that FSH, but not LH, is involved in the development of meiotic competence. Further, this action of FSH appears to be mediated, at least partially, by follicular oestrogen production.

Animals↗
PubMed1983

Decrease in blood and ovarian 3 alpha- and 3 beta-androstanediol levels in rats induced to ovulate with pregnant mare serum gonadotropin.

Several hours before the first ovulation progesterone metabolism in the rat ovary, in vitro, is shifted from the production of 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) as the major metabolite toward the production of 4-ene-3-oxosteroids. In the present paper, changes in levels of 3 alpha-diol and its 3 beta-epimer as well as testosterone in blood and ovaries around the time of the first ovulation have been studied in immature PMSG-treated rats. Forty-eight hours after PMSG, a considerable increase in blood and ovarian testosterone concentration was observed, whereas the concentrations of both androstanediols in blood decreased sharply. At 52 h, the level of ovarian 3 beta-diol was only one third of the control level and continued to fall. The decrease in ovarian 3 alpha-diol was less pronounced, but reached about half, or less, of the control value. In PMSG-treated rats in which the LH surge was blocked by pentobarbitone, the decrease in blood diols was delayed but not prevented. It is concluded that the decrease in production of the androstanediols preceding the first ovulation observed previously in isolated ovaries, also occurs in the intact rat. The decrease in androstanediols occurs very shortly before an ovulation induced with an injection of PMSG and is dependent on the occurrence of an LH surge. Since it is assumed that the androstanediols have a prepubertal role in inhibiting uterine and ovarian growth and in preventing cyclic LH release, it is essential that their concentration decrease several hours before the first ovulation.

Androstane-3,17-diol↗
PubMed1982

Photoaffinity-labeling and fluorescence-distribution studies of gonadotropin-releasing hormone receptors in ovarian granulosa cells.

Photoaffinity labeling of rat ovarian granulosa cells and membrane preparations with a bioactive photoaffinity derivative of gonadotropin-releasing hormone resulted in identification of two specific components with apparent molecular weights of 60,000 and 54,000. Fluorescent visualization of gonadotropin-releasing hormone receptors in these cells, by using a bioactive rhodamine derivative of the hormone, indicated that the fluorescently labeled receptors were initially distributed uniformly on the cell surface and then formed patches that subsequently internalized (at 37 degrees C) into endocytic vesicles. These processes were dependent on specific binding sites for the rhodamine-labeled peptide on the granulosa cells. These studies may provide an experimental basis for understanding the molecular events involved in the action of the hormone in the ovary.

Affinity Labels↗
PubMed1981

On the synergistic action of androgen and FSH on progestin secretion of cultured rat granulosa cells. Cellular and mitochondrial cholesterol metabolism.

The effect of FSH and androgen on the conversion of cholesterol into progesterone by cultured rat granulosa cells (GC) was studied in intact cells or mitochondrial preparations. Culture of GC for immature hypophysectomized diethylstilbestrol-treated rats for 48 h in the presence of ovine FSH (5 microgram/ml) alone, or FSH + testosterone (Te; 0.5 microgram/ml) caused a slight increase in the activity of the mitochondrial marker enzyme succinic dehydrogenase, while Te had no effect. Culture with the hormones for 48 h had no significant effect on the levels of free and esterified cellular cholesterol. GC monolayers after 48 h with or without FSH and Te converted [3H]cholesterol into 4 major metabolites, 3 of which were secreted into the medium and, in thin-layer chromatographic behavior, resembled pregnenolone, progesterone and 20 alpha-dihydroprogesterone. The total amount of the 3 C-21 steroids was higher (p less than 0.01) in FSH- or Te-treated than in control cells, and combined treatment had a synergistic effect. The uptake of labeled cholesterol (4--10%) was significantly higher (p less than 0.01) in cells pretreated with FSH or Te, whereas a combined FSH and Te treatment had an additive effect. Mitochondria isolated from GC monolayers took up cholesterol in a temperature-dependent fashion, but this uptake was not affected by hormonal pretreatment. In the presence of cyanoketone, the mitochondrial fractions activity converted cholesterol into pregnenolone. This activity was enhanced by FSH or Te (p less than 0.01), and further enhancement was observed with FSH + Te; the combined effect appeared to be more than additive (p = 0.05). The results suggest that both FSH and Te enhance the activity of cholesterol side-chain cleavage, but do not affect the transport of cholesterol into the mitochondria. A possible hormonal effect on a pre-mitochondrial step is discussed.

Animals↗
PubMed1980

Aggregation of luteinizing hormone receptors in granulosa cells: a possible mechanism of desensitization to the hormone.

The temporal relationship between redistribution of receptors to lutropin (luteinizing hormone)/human chorionic gonadotropin in cultured rat ovarian granulosa cells and the cellular response to hormonal challenge were studied. Visualization of receptor-bound human chorionic gonadotropin by indirect immunofluorescence, with hormone-specific antibodies after fixation with 2% formaldehyde, revealed the existence of small clusters around the entire cell circumference 5--20 min after exposure to the hormone at 37 degrees C. Such small receptor aggregates were also evident if hormone incubation was at 4 degrees C or if cells were fixed with 2% formaldehyde before incubation. Larger clusters were evident after prolonged incubation with the hormone (2--4 hr) at 37 degrees C. The later change coincided with diminished cyclic AMP accumulation in respose to challenge with fresh hormone. When the fixation step was omitted and antibodies to human chorionic gonadotropin were applied after hormonal binding, acceleration of both receptor clustering and the desensitization process was observed. This maneuver also induced capping of the hormone receptors. In contrast, monovalent Fab' fragments of the antibodies were without effect. Internalization of the bound hormone in lysosomes, and subsequent degradation, was evident 8 hr after hormonal application and was not accelerated by the antibodies. It is suggested that clustering of the luteinizing hormone receptors may play a role in cellular responsiveness to the hormone. Massive aggregation of the receptors may desensitize the cell by interferring with coupling to adenylate cyclase.

Adenylyl Cyclases↗
PubMed1979

Effect of human chorionic gonadotropin and prolactin on 20 alpha-hydroxysteroid dehydrogenase activity in granulosa cells of immature rat ovary.

The effects of FSH, hCG, and PRL on the activity of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-SDH) of separate ovarian components of hypophysectomized, diethylstilbestrol-treated rats were studied. Enzyme activity was found to reside mainly in granulosa cells. FSH induced an increase in enzyme activity. A preparation of FSH was purified by adsorbing its LH contamination on rat corpora lutea membranes and by further neutralizing LH traces with an antiserum to the beta-subunit of LH. This purified FSH retained the ability to induce a 6-fold increase in specific enzyme activity in granulosa cells of hypophysectomized, diethylstilbestrol-treated rats. Administration of hCG to rats treated with purified FSH, further enhanced 20 alpha-SDH activity in granulosa cells up to 11.5-fold above control. PRL, which is known to inhibit 20 alpha-SDH activity in regressing rat corpora lutea, suppressed the FSH-induced increase in enzyme activity in the granulosa cells.

20-Hydroxysteroid Dehydrogenases↗