Effects of Hypophysectomy and Administration of Cortisone or ACTH on Adrenal 5α-Reductase Activity and Steroid Production1

Kitay, Julian I.; Coyne, Mary D.; Swygert, Nancy H.

doi:10.1210/endo-89-2-432

Cited by 22 publications

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“…On the other hand, the influence of hypothyroidism upon the adrenal gland may be indirect. For example, hypothyroidism is known to depress synthesis and release of growth hormone (Geel & Timiras, 1970;Eisenberg, Sorrentino & Knigge, 1972;Kikuyama, Nagasawa, Yanai & Yamanouchi, 1974;Froelich & Meserve, 1979) and gonadal hormones (Leathern, 1972) which are necessary for ACTH to stimulate the adrenal cortex properly (Kitay, Coyne & Swygert, 1971;Colby, Caffrey & Kitay, 1973; Colby & Kitay, 1974;Colby, Malendowicz, Caffrey & Kitay, 1975;Kramer, Greiner & Colby, 1977;Colby, 1978). Before conclusive statements can be made regarding the influence of other hormones, the sequential development of hypothalamic secretory competence, pituitary hormone output and adrenocortical structural integrity remain to be determined in rats made hypothyroid by administration of thiouracil from conception.…”

Section: Discussionmentioning

confidence: 99%

Development of Hypothalamic–pituitary–adrenal Response to Stress in Rats Made Hypothyroid by Exposure to Thiouracil From Conception

Meserve¹,

Leathem²

1981

Journal of Endocrinology

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The functional maturation of the hypothalamic-pituitary-adrenal (HPA) axis has been studied in rats of 20-35 days of age made hypothyroid by the administration of thiouracil from conception. Basal concentrations of corticosterone in serum were normal in hypothyroid animals. Ether stress led to an increase corticosterone content of the adrenal glands of hypothyroid and normal rats but not to a rise in serum corticosterone of hypothyroid rats until 30 days of age. Corticosterone secretion in response to ACTH administration was subnormal in hypothyroid rats. The hypothyroid state delays the development of the hypothalamic-pituitary-portion of the HPA axis until 30 days of age and causes a diminution in adrenal response to ACTH beyond this time.

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Section: Discussionmentioning

confidence: 99%

Development of Hypothalamic–pituitary–adrenal Response to Stress in Rats Made Hypothyroid by Exposure to Thiouracil From Conception

Meserve¹,

Leathem²

1981

Journal of Endocrinology

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“…A secondary inhibition of the activity of the enzyme might be expected in the intact rat since progesterone apparently decreases both estrogen and ACTH secretion as noted above; both these hormones suppress adrenal 5a-reductase activity (2,27). However, the observed changes in uterine and adrenal weight seen in the progesterone-treated intact rats were small.…”

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confidence: 80%

The Influence of Progesterone on Adrenocortical Function in the Rat

Rodier

Kitay

1974

Experimental Biology and Medicine

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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...

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“…These investigations were supported by research grants from the NIH (AM03370) and NSF (GB41215). lism (7). Following hypophysectomy, adrenal 5a-reductase activity increases, resulting in enhanced conversion of corticosterone to 5a-dihydrocorticosterone (DHB) and 3/3,5a-tetrahydrocorticosterone (R) by adrenal homogenates in vitro.…”

mentioning

confidence: 99%

“…Following hypophysectomy, adrenal 5a-reductase activity increases, resulting in enhanced conversion of corticosterone to 5a-dihydrocorticosterone (DHB) and 3/3,5a-tetrahydrocorticosterone (R) by adrenal homogenates in vitro. Replacement of hypophysectomized rats with ACTH restores enzyme activity toward control levels (7,8). Little, however, is known about the relationship between the actions of ACTH on adrenal 5a-reductase activity, as measured in vitro, and its effects on steroid secretion in vivo.…”

mentioning

confidence: 99%

Role of Adrenal 5a-Reductase Activity in Determining the Responsiveness of Hypophysectomized Rats to ACTH

Colby

Malendowicz

Caffrey³

et al. 1975

Endocrinology

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Studies were conducted to examine the contribution of adrenal 5alpha-reductase to the phenomenon of diminished adrenal "responsiveness" to ACTH after hypophysectomy in rats. Rats hypophysectomized for 1 week secreted small amounts of corticosterone (B), 5alpha-dihydrocorticosterone (DHB) and 3beta,5alpha-tetrahydrocorticosterone (R) acutely after ACTH. Adrenal reductase activity in vitro at that time was high. After replacement with ACTH for 24 h, B,DBH, and R secretion increased slightly. Reductase activity remained high. Treatment with ACTH for 2 days further stimulated secretion of DHB and R but not B. Reductase activity was unaffected. Enzyme activity declined at 3 days concomitant with a proportionately greater increase in B than DHB and R secretion. Only after 7 days of ACTH did B secretion exceed DHB and R output. At that time, reductase activity was still lower. The results establish the functional significance of 5alpha-reductase activity as a regulatory site for the action of ACTH in determining the composition of adrenocortical secretory products in hypophysectomized rats.

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Effects of Hypophysectomy and Administration of Cortisone or ACTH on Adrenal 5α-Reductase Activity and Steroid Production1

Cited by 22 publications

References 0 publications

Development of Hypothalamic–pituitary–adrenal Response to Stress in Rats Made Hypothyroid by Exposure to Thiouracil From Conception

Development of Hypothalamic–pituitary–adrenal Response to Stress in Rats Made Hypothyroid by Exposure to Thiouracil From Conception

The Influence of Progesterone on Adrenocortical Function in the Rat

Role of Adrenal 5a-Reductase Activity in Determining the Responsiveness of Hypophysectomized Rats to ACTH

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