The Influence of Progesterone on Adrenocortical Function in the Rat

Abstract

Estradiol and testosterone have differing influences on adrenal function. Estradiol augments adrenal corticosterone secretion by increasing ACTH secretion (1) and decreasing intraadrenal reduction of corticosterone through inhibition of adrenal 5a-reductase activity ( 2 ) . Estradiol also stimulates hepatic metabolism and clearance of corticosterone ( 3 ) . In contrast, testosterone inhibits ACTH secretion (4), but also facilitates adrenal corticosterone secretion through inhibition of adrenal 5a-reductase activity ( 2 ) . Hepatic metabolism of corticosterone is suppressed by testosterone ( 5 ) . These differences in pituitary, adrenal, and hepatic responses to testosterone and estrogen probably account for the sex differences in adrenal function seen in the rat (6).The effects of progesterone on adrenal function are not as well understood as those of the other gonadal hormones. Several authors have reported that progesterone decreases adrenal corticosterone secretion ( 7 ) and adrenal weight ( 7 , 8) when administered to female rats in doses exceeding 5 mg/day. Plasma corticosterone after ACTH treatment has been reported to be diminished after treatment with doses as low as 2 .O mg/day ( 9 ) . In contrast, Telegdy et al. have shown that progesterone administered at a dose of 1.5 or 1.0 mg/day increases adrenal corticosterone secretion ( 7, 10) and adrenal weight ( 7 ) . Ultrastructural changes in the fasciculata, reticularis, and glomerulosa of the adrenal cortex of female animals treated with progesterone ( 1 .O mg/ day) have been interpreted by Volk (1 1) to indicate hyperactivity of these structures. Givner and Rochefort ( 1 2 ) have recently reviewed and extended the data concerning the effects of synthetic progestogens on adrenal function in female rats. The most intensively studied of these, 6 alpha-methyl-pregn-4-en-3, 20 dione-1 7-acetate (medroxyprogesterone) , has usually been reported to produce adrenal atrophy, decreased plasma corticosterone concentration, and decreased in vitro corticosterone production. These effects have been ascribed in part to a block of pituitary ACTH secretion. Studies of the effect of progestogens on the adrenal function of ovariectomized animals are relatively few and contradictory.Edgren et al. (13) have reported that progesterone or 6-methyl-17 acetoxyprogesterone administration at a dose of 1 mg/day caused a decrease in adrenal weight of spayed females. In another experiment, only the latter preparation was effective. Brennen and Kray (14) found no significant effect of progesterone on adrenal weight when administered at either 1 .O or 3.0 mg/day to ovariectomized rats. The limited evidence concerning progesterone effects on male adrenal function indicates that injection of 10 mg/day results in decreased adrenal corticosterone secretion (9, 1 5 ) without a significant change in adrenal weight (15). In contrast, doses ranging from 0.3 rng to 3 mg/day caused increased adrenal weightThe experiments reported here were undertaken to determine if progesterone exerts an influ...

A Method to Study Temporal Changes in Adrenal Activity in Relation to Sexual Status in the Female Laboratory Rat

“…Such a result argues in favour of a reduction in the level of ACTH by progesterone (Rodier & Kitay, 1974), a conclusion which gains strength from results in stressed rats where injection of progesterone with or without oestrogen resulted in a significant fall in the concentration of corticosterone in adrenal venous plasma to approximately the level observed in ovariectomized rats. In contrast, administration of oestrogen to ovariectomized rats brings the values obtained during stress to within the range found in the normal cyclic animal and close to the values obtained at pro-oestrus when secretion of oestrogen by the ovary is believed to be at its highest (Tapper & Brown-Grant, 1975).…”

“…Investigations into the relationship between the ovary and the adrenal cortex have been based on the changing activity of the adrenal gland (as expressed by the levels of cortico¬ steroids in the peripheral circulation or adrenal venous blood) during the stages of the oestrous cycle (Dean, Cole «fe Chester Jones, 1959;Telegdy, Huzar, Endröczi & Lissak, 1962;Critchlow, Liebelt, Bar-Sela, Mountcastle & Lipscomb, 1963;Kitay, 1963a, b;Pincus & Hirai, 1964;Hess & Reigle, 1970;Raps, Barthe & Desaulles, 1971; Rodier & Kitay, 1974;Ramaley, 1975; Ogle & Kitay, 1977). Any understanding of the relationship between the level of corticosteroids in adrenal venous blood and ovarian function must recognize the complicating factor of stress ; the studies cited above have failed to eliminate the stress of prolonged surgical interference.…”

Suppression of Cortisol Levels in Subordinate Female Marmosets: Reproductive and Social Contributions

“…Progesterone seems unlikely to account for the observed cortisol difference between subordinate and ovariectomized animals. Although its effects on HPA activity are not well understood, numerous reports suggest that progesterone either suppresses or does not alter circulating glucocorticoid levels (e.g., Ganong, 1963;Rodier and Kitay, 1974;Phillips and Poolsanguan, 1978). Clearly, these effects cannot account for the finding that subordinate females had both lower progesterone levels and lower cortisol levels than ovariectomized (and cycling) females.…”

Adrenal toxicology: a strategy for assessment of functional toxicity to the adrenal cortex and steroidogenesis

“…Oestrogen is known to stimulate ACTH (Barrett, 1960) and therefore adrenocortical function, whilst progesterone is reported to inhibit adrenocortical function in the rat (Rodier and Kitay, 1974). Gonadotrophins, melanocyte stimulating hormone and prolactin both alone and synergistically with oestrogen, have been reported to stimulate corticosterone in the rat (Sugihara et al, 1982;Vinson et al, 1976;Vasquez and Kitay, 1978;Ogle and Kitay, 1979).…”

“…• Stage of the oestrous cycle should be assessed if females are used, as this affects adrenocortical status (Ogle and Kitay, 1979;Nicholls and Chevins, 1981) as does oestrogen (Barrett, 1960) and progesterone (Rodier and Kitay, 1974), and group sizes need to be adequate because of individual variability in hormones.…”