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Biomedical subjects

H Guo

Publications and source records attributed to H Guo.

At least 307 records · Page 17Linked to original sources
PubMed1991

Recombinant monocyte-derived interleukin-1 receptor antagonist reverses inhibitory effects of interleukin-1 on Leydig cell steroidogenesis.

Previously we have reported that interleukin-1 (IL-1) is a potent inhibitor of Leydig cell function. Most recently, IL-1 receptor antagonist (IL-1ra) has been purified, sequenced and cloned. In the present study, we evaluated the recombinant monocyte-derived IL-1ra on the inhibitory effects of IL-1. The addition of recombinant human IL-1ra up to 1000 ng/ml has no discernible effects on human chorionic gonadotropin (hCG)-stimulated testosterone formation in primary cultures of rat Leydig cells. Similar to that reported previously, IL-1 beta caused a dose-dependent inhibition of hCG-induced testosterone. The inhibitory effect of IL-1 beta could be reversed by the concomitant addition of IL-1ra. The amounts of IL-1ra required to reverse the effect of IL-1 were 25-fold higher. Our results suggest that IL-1 is important in modulating Leydig cell function and its effect most likely is mediated by specific IL-1 receptors.

Animals↗
PubMed1990

Drosophila RNA polymerase II elongation factor DmS-II has homology to mouse S-II and sequence similarity to yeast PPR2.

DmSII is a Drosophila RNA polymerase II elongation factor which suppresses pausing by RNA polymerase II at specific sites on double stranded templates. Using antibodies produced against the purified protein, a Drosophila cDNA expression library was screened and a cDNA was isolated which encoded a portion of DmSII. When this cDNA was used to probe Kc cell mRNA the predominant species was found to be 1.4 kb in length. The original cDNA was used to screen a Drosophila Kc cell cDNA library resulting in the isolation of a 1.4 kb cDNA which was then sequenced. The deduced protein sequence for DmSII exhibited high similarity to mouse SII protein sequence. In addition, significant sequence similarity was found with the protein encoded by the yeast gene PPR2, which is involved in regulation of URA4 gene expression. The comparison of amino acid sequences suggests that DmSII is comprised of two domains homologous to mouse SII separated by a flexible, serine rich region of low homology. The shorter yeast protein has sequence similarity only to the carboxy terminal domain.

Amino Acid Sequence↗
PubMed1990

Regulation of insulin-like growth factor-I messenger ribonucleic acid expression in Leydig cells.

In the present study, we evaluated insulin-like growth factor-I (IGF-I) messenger RNA expression in the rat testis. Crude interstitial cells were separated into three distinct bands on 15-60% Percoll density gradients. IGF-I mRNA was mainly localized in the Leydig cell-enriched fraction (band 3), while band 1 and band 2 cells did not contain significant amounts of IGF-I mRNA. Leydig cell IGF-I mRNA consisted of multiple species varying from 0.8 to 7.5 kb and was present in rat Leydig cells all ages examined, from 25 to 55 days old. To further document that IGF-I mRNAs are present in Leydig cells, the method of Klinefelter et al. (Biol. Reprod. (1987) 36, 769-783) was used to isolate highly purified (greater than 98% pure) Leydig cells. Most of the IGF-I mRNA was localized in these Leydig cells, while there was no detectable IGF-I mRNA in the whole testis or other interstitial cells. Furthermore, IGF-I mRNA in Leydig cells was increased more than 2-fold by growth hormone (GH) administration in vivo. This suggests that IGF-I mRNA in Leydig cells is also GH dependent. Interstitial IGF-I produced in Leydig cells may have both autocrine and paracrine effects in the testis.

Animals↗
PubMed1990

Differential effects of recombinant interleukin-1 alpha and beta on Leydig cell function.

Previously we have reported that human chorionic gonadotropin(hCG)-stimulated testosterone biosynthesis was markedly inhibited by purified natural human interleukin-1 (IL-1). In the present study we evaluated the effects of human and murine recombinant IL-1 (rIL-1) on Leydig cell steroidogenesis in primary culture. Human rIL-1 beta caused a dose-dependent inhibition of hCG-, 8-bromo cyclic AMP-, and forskolin-induced testosterone formation. In contrast, human rIL-1 alpha was considerably less potent. When the effects of the cytokines were corrected for their biological potencies, human rIL-1 beta and murine rIL-1 alpha were still more effective than human rIL-1 alpha in inhibiting testosterone production (at least 100-fold more potent). Thus, even though IL-1 alpha and IL-1 beta bind to the same receptors on T cells, Leydig cells exhibit differential sensitivity in response to rIL-1 alpha and rIL-1 beta which is partly species dependent.

Animals↗
PubMed1990

Tumor necrosis factor-alpha enhances inhibitory effects of interleukin-1 beta on Leydig cell steroidogenesis.

Human recombinant tumor necrosis factor-alpha (rTNF alpha) alone (up to 1000 units/ml) did not alter either basal or human chorionic gonadotropin (hCG)-induced testosterone formation in primary culture of rat Leydig cells. However, concomitant addition of rTNF alpha with human recombinant interleukin-1 beta (rIL-1 beta) enhanced the inhibitory effects of rIL-1 beta. The rIL-1 beta dose response curve was shifted to the left (IC50 changed from 1 ng/ml to 0.3 ng/ml). Even though rTNF alpha had no effect on testosterone formation, hCG-stimulated cyclic AMP formation was inhibited by rTNF alpha in a dose dependent manner. In the presence of both rTNF alpha and rIL-1 beta, hCG-induced cyclic AMP formation and binding of [125I]-hCG to Leydig cells were further inhibited. Testicular macrophages represent about 20% of the interstitial cells. TNF alpha and IL-1 may be produced locally by interstitial macrophages and have paracrine effects on Leydig cell function.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Interleukin-2 is a potent inhibitor of Leydig cell steroidogenesis.

Interstitial tissue of the testis consists of Leydig cells, macrophages, lymphocytes, plasma cells, mast cells and fibroblasts. Previously we have reported that interleukin-1 (IL-1) inhibits Leydig cell androgen production. In the present study, the effect of IL-2 was investigated. Leydig cells (10(5) cells/ml) from adult Sprague-Dawley rats were cultured with or without IL-2 for 24 h. After medium changes, human CG (hCG), 8-bromo-cAMP, or forskolin was added with or without IL-2. Cultures were continued for an additional 24 h, and testosterone and cAMP levels were measured. IL-2 up to 100 U/ml had no effect on basal testosterone production. hCG-stimulated testosterone formation was inhibited in a dose-dependent manner by the addition of IL-2. IL-2 in a concentration of 100 U/ml decreased hCG-induced testosterone formation from 49.6 +/- 3.6 ng/ml (mean +/- SE) to 8.5 +/- 4.2 ng/ml. The hCG dose-response curve was shifted to the right by the addition of IL-2. Maximal testosterone production in response to hCG was reduced 40% in the presence of IL-2 (50 U/ml) without alteration of median effective dose (ED50). IL-2 also inhibited hCG-induced cAMP formation and 8-bromo cAMP- and forskolin-stimulated testosterone production. However, IL-2 did not alter the binding of [125I]hCG to purified Leydig cells. Furthermore, IL-2 significantly inhibited the conversion of 20-OH-cholesterol, 22-OH-cholesterol, pregnenolone, progesterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone to testosterone but did not alter the conversion of dehydroepiandrosterone and androstenedione to testosterone. Our results suggest that a T cell growth factor, IL-2, is a potent inhibitor of steroidogenesis. IL-2 may play a paracrine role in modulating Leydig cell function.

8-Bromo Cyclic Adenosine Monophosphate↗