The Aging Leydig Cell VIII Protein Kinase Activity

Abstract

The effects of aging on cyclic AMP (cAMP) dependent protein kinase activity of purified Leydig cells were evaluated. Purified Leydig cells from 20-day-, 40-day-, 60-day- and 30-month-old rats were incubated with or without hCG for 1 hour. At the end of incubation, tubes were centrifuged and supernatants were saved for cAMP and testosterone determinations, and the pellets were prepared for protein kinase assay. Basal cAMP levels of Leydig cells from 20-day- and 40-day-old rats were lower than those of 60-day- and 30-month-old rats. In response to hCG stimulation, Leydig cells of 40-day-old rats produced the highest amounts of cAMP, while 30-month-old had the lowest levels. Testosterone responses of 30-month-old rates were also significantly lower than those of 60-day-old mature rats. When cAMP-dependent protein kinase activities were measured, 30-month-old rats had the lowest total kinase activity. These results suggest that reduced protein kinase activity might contribute to the decreased testosterone synthesis of aged rats.

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

“…In addition, gonadotropin stimulation of cAMP production and PKA activity in Leydig cells was unaffected by the aging process [182,183,186]. Two reports, however, have provided evidence suggesting that aging negatively impacts on cAMP production and cAMP-stimulated PKA activity in Leydig cells and that such reduction in the cAMP signaling cascade may be functionally linked to decreased testosterone synthesis and secretion seen with advancing age [189,190]. On the other hand, studies from our laboratory indicate that testosterone secretory response to LH (endogenous gonadotropin), cholera toxin (a nonspecific stimulator of adenylate cyclase), forskolin (stimulator of adenylate cyclase) and cAMP agonists (e.g., Bt 2 cAMP, 8Br-cAMP, 8CPT-cAMP), like hCG, is reduced by 60-70% in purified Leydig cells from older animals [183].…”

Leydig cells: From stem cells to aging

“…Thus, in vitro studies have shown that, in response to LH, Leydig cells isolated from the testes of aged rats produce less testosterone than cells from young adults (Chen et al, 1994; Zirkin et al, 1993; Liao et al, 1993). Among the age-related changes in the steroidogenic pathway that could be responsible for the reduced ability of the aged cells to production testosterone compared to young cells are reduced LHR number, cAMP production, and/or PKA activity (Chen et al, 2002; Lin et al, 1983). There is evidence that cholesterol transport mechanisms also are compromised in aged Leydig cells (Liao et al, 1993; Culty et al, 2002).…”

The Emerging Pathophysiology of Age‐related Testicular Degeneration with a Focus on the Stallion and an Update on Potential Therapies

“…1994). Researchers have identified several differences in aged Leydig cells that could adversely affect the function of the steroidogenic pathway, including differences in LH‐receptor number, cAMP production, PK‐A activity, cholesterol transport and activities of steroidogenic enzyme (Lin et al. 1983; Liao et al.…”

“…The decline in testosterone is not because of a decline in Leydig cell number, but rather is the result of a loss of steroidogenic function in the old Leydig cells (Chen et al 1994). Researchers have identified several differences in aged Leydig cells that could adversely affect the function of the steroidogenic pathway, including differences in LHreceptor number, cAMP production, PK-A activity, cholesterol transport and activities of steroidogenic enzyme (Lin et al 1983;Liao et al 1993;Luo et al 1996Luo et al , 2005Chen et al 2002;Culty et al 2002).…”