dc.contributor.author | Hipkin, Richard William George. | en_US |
dc.date.accessioned | 2014-10-21T12:35:04Z | |
dc.date.available | 1991 | |
dc.date.issued | 1991 | en_US |
dc.identifier.other | AAINN71483 | en_US |
dc.identifier.uri | http://hdl.handle.net/10222/55263 | |
dc.description | The goal of the studies in this thesis was to characterize the role of second messenger interactions in regulation of androgen (T) output by the Leydig cell (LC). | en_US |
dc.description | Analogues of cyclic adenosine 3$\sp\prime,5\sp\prime$-monophosphate (cAMP) selective for either binding site (S1 and S2) on the regulatory subunits of cAMP-dependent protein kinases (PK-A) were used to assess the role of type 1 (T1) and type 2 (T2) PK-A in LC function. As S1 and S2 exhibit positive cooperativity, coexposure to analogue pairs will synergistically increase T output should T1 or T2 PK-A be present. Both T1 and T2 PK-A were active in the LC, though T1 PK-A activity was predominant. Coincubation with cAMP, luteinizing hormone (LH) or forskolin also synergistically increased T though the response with forskolin was reduced suggesting cAMP-independent activities. | en_US |
dc.description | Although atrial natriuretic factor (ANF) stimulates T output via cyclic guanosine 3$\sp\prime,5\sp\prime$-monophosphate (cGMP), coexposure of LC to ANF and LH or ANF/cGMP and the same cAMP analogues resulted in a synergistic increase in T production suggesting cyclic nucleotide interaction mediates a cooperative hormonal control of the mouse LC in vivo. | en_US |
dc.description | The role of calmodulin (CaM) in LC function was assessed using a CaM antagonist, N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W7) and a multichambered cell perifusion system. Exposure to W7 caused an initial nonspecific inhibition followed by a CaM-dependent increase in T synthesis suggesting the presence of a novel inhibitory CaM-sensitive process in the LC. The response did not involve inhibition of a CaM-dependent phosphodiesterase (PDE) but could be abolished with a phospholipase A$\sb2$ inhibitor and mimicked by a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). The response to W7 and NDGA co-infusion was not additive, suggesting a common mechanism of action, possibly mediated by arachidonic acid. | en_US |
dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 1991. | en_US |
dc.language | eng | en_US |
dc.publisher | Dalhousie University | en_US |
dc.publisher | | en_US |
dc.subject | Biology, Cell. | en_US |
dc.subject | Biology, Animal Physiology. | en_US |
dc.subject | Chemistry, Biochemistry. | en_US |
dc.title | The role of second messenger interactions in the control of androgen production in the mouse Leydig cell. | en_US |
dc.type | text | en_US |
dc.contributor.degree | Ph.D. | en_US |