Inhibitors of adenylate cyclase from ejaculated human spermatozoa

Haesungcharern, Audomsark; Chulavatnatol, Montri

doi:10.1530/jrf.0.0530059

Cited by 13 publications

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“…Recent studies have described the activation of sperm adenylate cyclase by an analogue of GTP in immature bovine spermatozoa [Casillas et al, 19801 and mature ram spermatozoa with the addition of the guanine nucleotide regulatory component from human erythrocyte membranes [Stengel and Hanoune, 19811. In some cells, the adenylate cyclase complex is stimulated by Ca2+ through the guanine nucleotide regulatory component [Jackowski et al, 1980;Rodbell, 19801, and detergent solubilization of the enzyme interferes with activators, such as fluoride [Johnson and Sutherland, 19731, which act through this component [Downs et al, 19801. Since there are few reports on human sperm adenylate cyclase [Gray et al, 197 1,1976;Haesungcharern and Chulavatnatol, 1978;Cheng and Boettcher, 19791, we investigated a number of potential activators of this enzyme, with emphasis on the possible regulation by Ca2+.…”

Section: Introductionmentioning

confidence: 99%

Calcium and adenosine affect human sperm adenylate cyclase activity

Hyne

Lopata

1982

Gamete Research

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The adenylate cyclase activity of human ejaculated spermatozoa in broken-cell preparations was investigated. In the presence of 5 mM metal cations and 0.1 rnM ATP, the relative enzyme activity with Mn", CaZ+, Mg2*, Ba2+ was 1.00, 0.28, 0.22, and 0.03, respectively. Added Ca2' appeared to activate the enzyme in the presence of MnZ* or MgZf, The human sperm adenylate cyclase was stimulated by -2-fold by free Ca*+ (1mM) in the presence of Mg2* (5 mM). If the G T P analogue, 5'-guanylyl imidophosphate (Gpp(NH)p) was added to the sperm homogenate in the presence of 200 pM ethylene-glycol-bis (0-aminoethylether) N,"-tetraacetic acid (EGTA), the adenylate cyclase activity was increased by approximately 25%, but with the addition of 280pM Ca2+ there was a decrease in enzyme activity. A similar response to low concentrations of Ca2' was obtained after complementation of the sperm enzyme with the guanine nucleotide regulatory component from human erythrocytes, where the addition of 40 pM Gpp(NH)p, 200 pM EGTA, and Ca2+ ( < 160 pM) stimulated the sperm enzyme -3-4-fold, but the further addition of CaL+ (280 pM, final) neutralized the stimulatory effect. The addition of adenosine, and the nucleotides 5/-AMP and 5/-ADP inhibited the enzyme, whereas guanine and 5'-GMP had no appreciable effect. Human follicular fluid and serum also had little direct effect on the sperm adenylate cyclase. These results suggest that Ca2+ might be an important physiological modulator of the human sperm adenylate cyclase.

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Section: Introductionmentioning

confidence: 99%

Calcium and adenosine affect human sperm adenylate cyclase activity

Hyne

Lopata

1982

Gamete Research

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“…These discrepancies may be due to species differences and/or experimental conditions. For instance, in Braun's experiments using bovine sperm, 5 mM of Zn2+ activated adenylate cyclase and acted synergistically with 5 mM of Ca2+ (2); whereas in Haesungcharern and Chulavatnatol's study using human sperm, 2.5 mM of Zn2+ showed pronounced inhibition of adenylate cyclase, but the enzyme was insensitive to Ca2+ (8). Furthermore, in studies (16) using human liver membranes, adenylate cyclase stimulated by either glucagon or fluoride was inhibited by Zn2+ (12.5-100 pM), but the effect of Ca2+ was not investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies indicate that the uptake of hCG in the testes of zinc-injected rats is significantly higher than that in controls (1 1, 12) and that Zn2+ affects adenylate cyclase activity in bovine and human sperm (2,8) and liver (16). We investigated that the effects of various divalent metal ions, including Zn2+, on cyclic AMP, cyclic GMP, and testosterone production stimulated by hCG and the effect of Zn2+ on the binding of [1251]hCG to rat testicular tissue in vitro.…”

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Effect of Zinc Ion on Human Chorionic Gonadotropin-Stimulated in Vitro Production of Cyclic AMP and Testosterone by Rat Testis

et al. 1984

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SummaryThis study explores the effects of several divalent metal ions on the in vitro production of cyclic AMP, cyclic GMP, and testosterone by rat testicular tissue and on the amount of binding of ['251]human chorionic gonadotropin (hCG) in the testis. Zn2+ at concentrations of to M enhanced the hCG-stimulated production of cyclic AMP and testosterone, but only in the presence of Ca2+. ['251]hCG binding to rat testicular tissue was not affected by Zn2+. Cu2+, Ni2+, Co2+, and MnZ+ did not increase cyclic AMP or testosterone production in concentrations of lo-' to M and even inhibited them at a high concentration M). Cyclic GMP production was not affected by these divalent ions. These results suggest that Zn2+ may play an important role in rat testicular steroidogenesis. Abbreviations hCG, human chorionic gonadotropin KRBB, Krebs Ringer bicarbonate buffer PBS, phosphate buffered saline Trace metal ions are known to influence hormones at several stages of action, including hormone secretion and activity and binding to target tissue. Conversely, hormones influence trace metal ion metabolism at several levels, including excretion and transport of ions (9). Zinc ion plays an important role in growth and sexual development. A deficiency of zinc not only reduces zinc levels in the reproductive tissues but also impairs the responsiveness of the Leydig cells to gonadotropins, and thus may cause primary hypogonadism in humans as well as in experimental animals (1, 14, 28). Furthermore, constitutionally short boys at Tanner stages 1 and 2 have lower zinc levels in their serum and hair and lower serum testosterone levels than those at Tanner stages 3 to 5 (3). These results suggest that the relative testosterone deficiency in constitutional growth delay may result in decreased zinc levels, which in turn could cause a further delay in sexual development and growth.Recent studies indicate that the uptake of hCG in the testes of zinc-injected rats is significantly higher than that in controls (1 1, 12) and that Zn2+ affects adenylate cyclase activity in bovine and human sperm (2, 8) and liver (16). We investigated that the effects of various divalent metal ions, including Zn2+, on cyclic AMP, cyclic GMP, and testosterone production stimulated by hCG and the effect of Zn2+ on the binding of [1251]hCG to rat testicular tissue in vitro. MATERIALS AND METHODSMale Wistar rats were reared in individual stainless steel cages and fed an adequate amount of zinc (43 ppm) ad libitum for 4 wk before the study. Deionized water was also provided ad libitum. The mean weight was 242 + 16 g at the time of study.They were anesthetized with ether. Both testes were removed, decapsulated, and sectioned into 50-mg slices from one rat for each experiment. Four tissue slices from each rat were used for each concentration of each metal in the presence or absence of hCG. Studies were repeated at least once and similar results were obtained in each metal experiment. This paper describes one of three similar zinc experiments. Sixteen rats were used in al...

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Observations on Cyclic Nucleotides in Human Semen

Mann

Jones

Sherins

et al. 1981

Journal of Andrology

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In agreement with earlier studies, we have found that the human seminal plasma yields considerably higher values for cyclic nucleotides when compared with spermatozoa. However, we have also shown that these values vary markedly both between different individuals and in specimens from the same individual at different times. Levels recorded for seminal plasma were 25 to 18, 937 nM of cyclic AMP and 0.54 to 3.57 nM of cyclic GMP. These levels were unrelated to those of either fructose (from the seminal vesicles) or zinc and citric acid (from the prostate). We have demonstrated also that in most specimens of seminal plasma the level of cyclic AMP remained stable during a 1‐hour incubation at 37 C or during prolonged storage at −40 C. Washed suspensions contained 13.2 to 27.2 pmol cyclic AMP/100 million spermatozoa. Adenylate cyclase activity of human semen was confined to the spermatozoa; it was several times higher in the presence of Mn2+ than Mg2+ and was unresponsive to sodium fluoride. The latter findings are consistent with enzyme activity derived from a dissociated catalytic component of adenylate cyclase.

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Inhibitors of adenylate cyclase from ejaculated human spermatozoa

Cited by 13 publications

References 4 publications

Calcium and adenosine affect human sperm adenylate cyclase activity

Calcium and adenosine affect human sperm adenylate cyclase activity

Effect of Zinc Ion on Human Chorionic Gonadotropin-Stimulated in Vitro Production of Cyclic AMP and Testosterone by Rat Testis

Observations on Cyclic Nucleotides in Human Semen

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