Regulation of activin A and inhibin B secretion by inflammatory mediators in adult rat Sertoli cell cultures.

The regulation of Sertoli cell activin A and inhibin B secretion during inflammation was investigated in vitro. Adult rat Sertoli cells were incubated with the inflammatory mediators, lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), IL-6 and the IL-1 receptor antagonist (IL-1ra) over 48 h in culture. Activin A, inhibin B and IL-1alpha were measured in the culture medium by specific two-site ELISAs. Both IL-1beta- and LPS-stimulated activin A and inhibited inhibin B secretion. LPS also stimulated the production of IL-1alpha in the cultures. In contrast to IL-1beta, IL-6 had no effect on activin A, although it did have a significant inhibitory effect on inhibin B secretion. Ovine follicle-stimulating hormone (FSH) and the cAMP analogue dibutyryl cAMP opposed the actions of IL-1 and LPS by suppressing activin A and IL-1alpha secretion and by stimulating inhibin B. Blocking IL-1 activity in the cultures by addition of an excess of IL-1ra completely prevented the response of activin A to exogenous IL-1beta, and reduced the response to LPS by 50%. In the presence of IL-1ra, basal secretion of inhibin B was increased, but IL-1ra was unable to reverse the suppression of inhibin B by LPS. These data indicate the importance of both IL-1 isoforms in regulating secretion of activin A and inhibin B by mature Sertoli cells during inflammation. The data also establish that inflammation exerts its effects on activin A and inhibin B secretion via other pathways in addition to those mediated by IL-1, and that hormonal stimulation by FSH and cAMP moderates the Sertoli cell response to inflammation. Interference with the complex interactions between these cytokines and hormones may contribute to the disruption of reproductive function that can accompany infection and illness in men.

Differential actions of gonadotropin-releasing hormone and human chorionic gonadotropin on interstitial fluid volume and immunoglobulin G concentrations in adult rat testis.

Gonadotropin-releasing hormone (GnRH) agonists regulate testicular interstitial fluid (tIF) volume, most probably via specific receptors on Leydig cells. The aim of this study was to confirm the interaction between GnRH and Leydig cells in regulation of testicular fluid, and to examine the effects on serum proteins in testis. Unilateral intratesticular injection of a GnRH agonist (100 ng/testis) caused a 50% reduction in tIF volume within 2 hours. Destruction of Leydig cells by treatment with ethane dimethane sulfonate also caused a similar decline in tIF volume; however, GnRH agonist treatment had no additional influence on this response in Leydig cell-depleted testes. GnRH agonist treatment had no effect on serum protein permeability in testis as indicated by maintenance of the tIF/serum immunoglobulin G (IgG) concentration gradient. Injection of human chorionic gonadotropin (hCG, 100 IU) had no effect on tIF volume at 2 hours, but increased the permeability of the testicular vasculature to serum IgG. At 20 hours after hCG injection, tIF volume was increased twofold, while the testicular permeability barrier to IgG appeared to have been restored. These data indicate that the acute inhibitory action of GnRH on vascular fluid permeability is dependent upon Leydig cells, confirming that these cells are the primary site of GnRH action on testicular vasculature. The data also indicate that supraphysiological doses of hCG cause a rapid increase in testicular permeability to serum proteins, which occurs prior to the well-characterized stimulation of tIF volume. These data provide further evidence that the concentration of serum proteins in tIF and the volume of tIF are both under regulatory control involving Leydig cells, but are independently regulated.

Regulation of interleukin 1alpha, activin and inhibin by lipopolysaccharide in Sertoli cells from prepubertal rats.

Bacterial lipopolysaccharide increased the production of interleukin 1alpha and activin A, and reduced production of inhibin B, in Sertoli cells from immature male rats measured by enzyme-linked immunosorbent assay (ELISA). The majority of immunoreactive interleukin 1alpha remained within the Sertoli cell, while both activin A and inhibin B were secreted. Lipopolysaccharide-stimulated expression of two interleukin 1alpha mRNA transcripts, measured by quantitative RT-PCR, but the levels of bioactive interleukin 1alpha in Sertoli cell extracts and medium, measured by in vitro bioassay, were comparatively low to undetectable. A specific antagonist of interleukin 1alpha had no effect on lipopolysaccharide-stimulated activin A or inhibin B responses. These data indicate that, in contrast to Sertoli cells from adult rats, lipopolysaccharide-induced regulation of activin A and inhibin B by prepubertal Sertoli cells does not involve secreted interleukin 1alpha. The data highlight the possibility of a role for intracellular interleukin 1alpha in the Sertoli cell response to inflammation, particularly in the immature testis.

Structure of chloro(dicyclohexylphenylphosphine)gold(I).

[AuCl(P(C6H5)(C6H11)2)), Mr = 506.8, orthorhombic, P2(1)2(1)2(1), a = 8.476 (5), b = 13.747 (2), c = 15.951 (3) A, V = 1858.8 (3) A3, Z = 4, Dx = 1.81 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 81.24 cm-1, F(000) = 984, T = 296 K, final R = 0.031 for 1860 unique observed reflections. The complex Cy2PhPAuCl adopts the two-coordinate linear geometry typical of AuI complexes. The P-Au-Cl angle is 178.3 (1) degrees while Au-P and Au-Cl distances are 2.234 (2) and 2.281 (3) A, respectively. The geometry of the P atom is tetrahedral with an average Au-P-C angle of 112.1 (3) degrees and an average P-C distance of 1.827 (8) A.

Structure of tris(dicyclohexylphenylphosphine)gold(I) perchlorate.

[Au(P(C6H11)2(C6H5))3][ClO4], M(r) = 1119.59, trigonal, R3c, a = 13.192(5), c = 52.83 (2) A, V = 7962 (9) A3, Z = 6, Dx = 1.401 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 29.5 cm-1, F(000) = 3468, T = 296 K, final R = 0.047 for 1321 unique observed reflections. The Au atom in the anion and the perchlorate ion in [Au(Cy2PhP)3][ClO4] lie on a threefold axis. The complex has an almost ideal trigonal-planar geometry, with an Au--P distance of 2.421 (3) A, P--Au--P angles of 119.9 (3) degrees, and the Au atom only 0.08 (2) A out of the plane defined by the three P atoms.

Structure of (2-benzoxazolethiolato)(triphenylphosphine)gold(I).

[Au(C7H4NOS)(C18H15P)], Mr = 609.7, monoclinic, P2(1)/n, a = 12.709 (3), b = 12.871 (4), c = 13.462 (6) A, beta = 94.64 (3) degrees, V = 2195 (2) A3, Z = 4, Dx = 1.84 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 68.7 cm-1, F(000) = 1176, T = 296 K, final R = 0.033 for 2823 unique observed reflections. The 2-benzoxazolethiolate ligand (Sboz), which contains three potential coordination sites (N, O and S), forms a linear complex with a P-Au-S angle of 176.43 (8). The Au-P and Au-S distances are 2.258 (2) and 2.299 (2) A, respectively. This angle and these bond distances are similar to those of other phosphorous-gold-sulfur complexes such as the antiarthritic drug auranofin.

Invariance of the pattern electroretinogram evoked by psychophysically equivalent stimuli in human ageing.

1. The aim of this study was to assess the contribution of retinal ganglion cells to the decline in contrast sensitivity during human ageing. 2. After determination of the appropriate refraction for each subject, younger subjects were arranged to be exposed to a display luminance which was suprathreshold by the same amount as in older subjects wearing a 4.0 mm diameter artificial pupil with a neutral density filter. 3. In fifty-four subjects, aged 20-99 years, contrast sensitivities measured in response to phase-reversed grating patterns of 2, 5 and 8 cycles per degree declined significantly with increasing age at each spatial frequency studied. 4. Subjects were made psychophysically equivalent by setting the display contrast at x5 and x10 contrast threshold for each subject. The pattern electroretinogram (PERG) was recorded with a sterile silver thread (DLT) electrode placed in the lower canthus of one eye, with the indifferent electrode on the temple and the earth on the forehead. 5. For each contrast multiple at each spatial frequency, the PERG implicit time showed no significant change with age, indicating equivalence of the response across the age range. 6. Control experiments with two young and two elderly subjects established that the PERG implicit time decreased appreciably with increasing contrast, over a range of x2 to x20 contrast threshold. 7. Since the psychophysically equivalent stimulus displays had generated equivalent PERGs in terms of implicit time in young and elderly subjects, this was consistent with the equivalence of retinal ganglion cell function under these conditions. 8. Adverse changes within the retina were therefore inferred to play a major role in the decline in contrast sensitivity with age.

Structure of tris(benzothiazole-N)trichlororhodium(III) nitromethane solvate.

mer-[RhCl3(C7H5NS)3].CH3NO2, Mr = 675.87, monoclinic, P21/n, a = 10.915 (2), b = 19.869 (4), c = 12.328 (3) A, beta = 103.13 (7) degrees, V = 2604 (1) A3, Z = 4, Dx = 1.724 g cm-3, lambda(Mo K alpha) = 0.71037 A, mu = 12.15 cm-1, F(000) = 1352, T = 298 K, final R = 0.0297 for 4459 unique observed reflections. The complex was prepared as part of a series of complexes of RhIII with heterocyclic ligands of the type RhL3X3. On the basis of spectral data alone, the assignment of the geometry as mer or fac and the mode of coordination through N or S were ambiguous, so the X-ray structure of the title complex was determined. The Rh is coordinated to three Cl and three N atoms to give an approximately octahedral, meridional complex. The potentially ambidentate benzothiazole coordinates to the metal through the N atom of the thiazole ring. The average Rh--N and Rh--Cl distances are 2.064 (5) and 2.34 (2) A, respectively.

Structure of a styrylbenzothiazole platinum(II) complex: [NEt4][PtBr3(asb)].

Tetraethylammonium tribromo[2-(2- acetoxystyryl)benzothiazole]platinate(II), [(C2H5)4N]-[PtBr3(C17H13NO2S)], Mr = 860.4 monoclinic, P21/c, a = 11.230 (9), b = 19.333 (4), c = 13.685 (6) A, beta = 101.06 (4) degrees, V = 2916 (4) A3, Z = 4, D chi = 1.96 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 90.3 cm-1, F(000) = 1648, T = 296 K, final R = 0.047 for 3384 unique observed reflections. The [PtBr3(asb)]- unit has square-planar geometry about the Pt, with the asb coordinated to the Pt through the N of the thiazole ring and a Pt-N bond distance of 2.010 (8) A. The average Pt-Br distance is 2.426 (7) A. The ligand is non-planar with a dihedral angle of 22.4 (7) degrees between the benzothiazole and the acetoxybenzene rings. The dihedral angles between the platinum coordination plane and the benzothiazole and benzene rings are 85.7 (1) and 71.3 (3) degrees respectively.

Structure of chlorobis(dicyclohexylphenylphosphine)gold(I).

[AuCl[C6H11)2(C6H5)P]2], Mr = 781.2, monoclinic, P2(1), a = 11.117 (4), b = 13.606 (5), c = 12.284 (4) A, beta = 109.59 (3) degrees, V = 1753 (2) A3, Z = 2, D chi = 1.48 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 43.8 cm-1, F(000) = 792, T = 296 K, final R = 0.024 for 3239 unique observed reflections. The formation of complexes of the type LnAuX, where L is a phosphine, and X is halide or pseudohalide, shows considerable dependence on the nature of the phosphine. When L = Ph3P, three- and four-coordinated complexes are very easily prepared. However, for L = Cy3P, only linearly coordinated complexes could be isolated. The geometry of the title complex, with L = CyPhP, is best described as distorted trigonal planar. The P-Au-P angle is 158.24 (5) degrees while the P-Au-Cl angles are 92.63 (6) and 108.71 (6) degrees. Au-P distances are 2.300 (1) and 2.324 (1) A while Au-Cl is 2.744 (2) A.

Structure of cis-Pt(asb)2Cl2, a platinum(II) complex with a styrylbenzothiazole ligand.

cis-Bis[2-(2-acetoxystyryl)benzothiazole]dichloroplatinum(II), [PtCl2(C17H13NO2S)2], Mr = 856.7, triclinic, P1, a = 12.145 (6), b = 12.859 (4), c = 11.021 (5) A, alpha = 105.88 (3), beta = 90.64 (4), gamma = 87.64 (4) degrees, V = 1654 (2) A3, Z = 2, D chi = 1.72 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 46.1 cm-1, F(000) = 840, T = 296 K, final R = 0.029 for 6121 unique observed reflections. The [PtCl2(asb)2] complex has square-planar geometry about the Pt, with the asb coordinated to the Pt through the N of the thiazole ring. The average Pt-N and Pt-Cl bond distances are 2.035 (1) and 2.287 (5) A. The ligand is non-planar with an average dihedral angle of 36 (3) degrees between the benzothiazole and the benzene rings. The dihedral angles between the platinum coordination plane and the benzothiazole and benzene rings are 78 (4) and 69 (7) degrees respectively. The acetoxybenzene rings in the two ligands have different orientations with respect to the olefin C atoms.