Cellular Localization of the Mn²⁺-Dependent Adenylyl Cyclase in the Human Testis

Abstract

An examination of the activity of the Mn2+-dependent adenylyl cyclase (AC) in fine needle biopsies from human testes was made. Simultaneously the DNA distribution patterns in suspensions of testicular cells derived from the same patients have been determined. The DNA distribution patterns were estimated by microflow fluorimetry (MFF) after staining with fluorochrome (ethidium bromide). Thus, AC activity could be assessed and correlated with the relative number of haploid (1C = spermatids), diploid (2C = spermatogonia and testicular somatic cells), and tetraploid (4C = primary spermatocytes) cells. Testicular Mn'+-dependent AC activities varied between 0 and 8.4 pmol cyclic adenosine monophosphate (cAMP)/mg proteidmin and were highly correlated with the contents of haploid (IC) germ cells (spermatids) (r = 0.62, p < 0.01). There was no correlation between Mn2+-dependent AC activity and diploid or tetraploid cells. This indicates that the Mn'+-dependent AC activity in the human testis, like in the rat and mouse, may be exclusively localized to haploid germ cells. An inverse correlation between plasma FSH and Mn'+-dependent AC activities indicated reduced inhibin secretion in situations where the Sertoli cells did not maintain the testicular germ cell production.

Calcium regulation of the soluble adenylyl cyclase expressed in mammalian spermatozoa

“…Furthermore, the sperm AC activity is stimulated by HCO 3 Ϫ , and had low affinity for ATP; all properties shared with recombinant sAC. Finally, two peaks of activity were recovered from gel filtration chromatography of the sperm extract, a finding similar to our previous observations in rat and other species (29,48,49). The first peak of activity comigrated with FL-sAC.…”

International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases

“…The initial observation was confirmed by several laboratories (Gordeladze and Hansson, 1981;Gordeladze et al, 1982;Stengel and Hanoune, 1984), but the nature of the enzyme catalyzing this reaction remained elusive for almost three decades. The unique properties of sAC were conclusively elucidated with the cloning of cDNAs derived from mouse testis and human embryonic kidney (HEK) 293 cells (Buck et al, 1999;Geng et al, 2005).…”

Cytosolic adenylyl cyclase defines a unique signaling molecule in mammals

“…Biochemical (3,10) and molecular ( Fig. 4B) evidence indicate sAC is preferentially expressed in testis and is very likely in post-meiotic germ cells (6,16,17) where the very high endogenous ATP concentration would support sAC activity. With its molecular isolation and functional heterologous expression, we now have the necessary tools to explore the biochemical regulation of sAC activity and ultimately determine its biological role.…”