Role of cortisol in the ACTH-induced suppression of testicular steroidogenesis in guinea pigs

Abstract

In order to investigate the role of cortisol in the regulation of testicular function, adult male guinea pigs were challenged with ACTH (20 IU), cortisol (8 or 16 mumol), or with ACTH plus dexamethasone (DEX, 2 mumol). The amounts of cortisol, testosterone, progesterone, and androstenedione present in the plasma or secreted by incubated adrenals or testes were determined by radioimmunoassay. The plasma concentrations of LH were determined using a radioimmunoassay for rat LH. ACTH treatment elevated cortisol plasma concentrations to 999% of control values, whereas it reduced testosterone plasma levels to 43% of control values. ACTH treatment did not affect LH plasma levels. A significant negative correlation was found in ACTH-treated animals, when the cortisol and testosterone plasma concentrations in serially taken blood samples (30-240 min after treatment) were compared (rs = -0.90 and rs = -0.99, P < 0.05). In addition to cortisol, ACTH raised progesterone and androstenedione plasma concentrations. If animals were treated with 2 mumol DEX + ACTH, the plasma levels of cortisol and androstenedione but not of progesterone, testosterone or LH were changed. ACTH stimulated the in vitro secretion of cortisol, progesterone and androstenedione by the adrenals but reduced the in vitro release of androstenedione and testosterone by the testes. In summary, treatment of guinea pigs resulted in elevated cortisol and in reduced testosterone plasma concentrations. The mechanism of the cortisol-induced inhibition of testicular function was independent of the LH plasma concentrations. The in vitro experiments indicate that cortisol directly interacts with the Leydig cells, presumably by inhibiting the activity of the testicular 17 alpha-hydroxylase and/or C17,20-lyase. Taking into account the results of comparable investigations in the rat, the inhibition of the testicular 17 alpha-hydroxylase and/or C17,20-lyase takes place if the intracellular cortisol exceeds the capacity of the 11 beta-hydroxysteroid dehydrogenase to inactivate it.

Hypoglycemia, But Not Insulin, Acutely Decreases LH and T Secretion in Men

“…It is known that a counterregulatory response of the HPA axis, including cortisol release, to hypoglycemia begins at normoglycemic ranges in poorly controlled type 2 diabetes (11), and the epinephrine response during hypoglycemia is enhanced (12). In vitro, glucocorticoids caused a decrease in LH and an increase in FSH in rat pituitary cells (13,14), and ACTH directly reduced T secretion in testicular cells of guinea pigs (15). In men, elevation of cortisol levels resulting from insulin-induced hypoglycemia or administration of hydrocortisone was followed by a rapid decrease in serum T levels without accompanying changes in LH secretion (8).…”

Cortisol influence on testicular testosterone secretion in domestic cat: An in vitro study

“…Additionally, Corticotropin Release Hormone (CRH) administration in the third ventricle stimulates LH secretion in a dose-dependent manner (Naylor et al 1990). On the other hand, Fenske (1997) performed in vitro studies showing that the mechanism of testicular function inhibition by cortisol does not depend on plasma LH concentrations since cortisol would be capable of acting directly on Leydig cells. This would probably occurs through inhibition of the enzymes 17 a-hydroxylase and/or C17,20 -lyase, thus indicating a specific action (local) on the testis.…”

“…Acute stress (Willemse et al 1993, Fenske 1997, Lacerda Neto et al 2004) such as the one undergone by group S, seems to sensitize the Leydig cells for an exacerbated response in the control condition (TCM 199 medium). Because pre-icubation (group C) and incubation with cortisol (groups A and C) does not alter testosterone secretion, it is probable that Leydig cell sensibilization under acute stress is not mediated by cortisol, but by some other mediator released during a stressful condition.…”

“…Despite evidences that stress exerts influence on reproductive functions, the interactions between the hypothalamus-pituitary-adrenal (HPA) and gonadal (HPG) axes remain unclear (Moberg 1991, Baldwin et al 1996, Fenske 1997, Ferasin 2001, Genaro et al 2003, Lacerda Neto et al 2004, Bridges et al 2005). There are indications of both inhibiting (Bambino & Hsueh 1981, Welsh et al 1982, Genaro et al 2003 and stimulating (Faulborn et al 1979, Welsh & Johnson 1981 effects of the HPA axis on HPG.…”

Enhanced 11beta-hydroxysteroid dehydrogenase type 1 activity in stress adaptation in the guinea pig

“…The total plasma cortisol concentration in unstressed animals ranges between 260 and 690 nmol/l (Fujieda et al 1982, Fenske 1997, and free cortisol concentrations are at least three times higher than in humans (Fujieda et al 1982). One reason for the high circulating cortisol concentration may be the low affinity of the guinea pig GC receptor to cortisol (Hodgson & Funder 1978, Kraft et al 1979.…”