Some effects of thyroxine administration on adrenal function in the rat

Vol . 7, Part I, pp. 891-896, 1968. Life Sciences Printed in Great Britain .

Pergamon Press

SOME 6FF~TS ~ THYROXINE ADMINISTRATION ON ADRFSIAL FUNCTION IN THF~ RAT Hsi-Chiang Chiu and Nicolas Zenker+ Department of Pharmaceutical Chemistry, School of Pharmacy University of Maryland, Baltimore, Maryland

(Received 29 April 1968; in final form 8 June 1968) In a recent review, T . S . Harrison (1) stated that hyperthyroidism similates adrenergic activity and, more specifically, the effects of epinephrine administration .

The determination of plasma epinephrine and

norepinephrine in rats receiving thyroid hormone (2) and of urinary epinephrine and norepinephL?ne levels in hyperthyroid patients (3) revealed not only an increase in total catecholamines but also an increase in the epinephrine to norepinephrine ratio . Since Eartly and L.eblond (4) indicated that thyroxine, in doses as small as six micrograms per rat per day for four weeks enhanced adrenal weight significantly in the thyioidectomized rat, and since the data of Wurtman (5) and more recently of Parker and Noble (6) suggested that the enzyme responsi5le for the norepinephrine to epinephrine conversion, phe~lethanolamine-N-methyl transferase (PNMT) varie3 largely in accordance with adrenal weight, it seemed appropriate to investigate whether administration of thyroxine would, in the normal as well as in the thyroidectamized rat, lead to an increase in adrenal weight and thereby also in PNMT .

Supported by NIH grant AM-06480 .

Preliminary data abstracted from

the thesis submitted by Miss Chiu for the M .S . degree in Pharmaceutical Chemistry .

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Further, since Wurtnan (5) demonstrated that adrenal medullary epinephrine synthesis was controlled by the adrenal cortex, it seemed of interest to explore the possibility that thyroid hormone might alter adrenocortical as well as adrenal medullary function .

Thyroxine

(Hlthrin

1N

~cperimental Sodium) was donated by Smith, IQine and French

Laboratoriess it was dissolved in alkaline saline (pit 8-9) for subcutaneous injections .

S-Adenosylmethionine 14CH 3 was obtained from the

New Sogland Nuclear Corporation and corticosterone from the Sigma Chemical Caapanyr .

Normal and thyroidectomized Sprague-Dawley male cats were

obtained from Hormone Assay Laboratories, Chicago, Illinois .

The ani-

male were sacrificed with a decapitator (Harvard Instrument Company) and the blood collected from their trunk portion (7) .

The adrenal glands

were dissected free frauu adhering tissue and placed on dry ice ;

they

were later weighed and processed in the fashion described by Wurtman (5 ) . Pherry lethanolanine-N-methyl tzansferase was assayed by a modification of the method of Wurtman and Axelrod (8) and the l 4C-metanephrine counted an a low background planchet counting system (Nuclear, Chicago) . Corticosterone was estimated by a modification of the method of Zenker and eernstein (9) which yielded a value of 2 .8 micrograms % for normal rat serum ; the final fluorcoetric measurements were carried out on an Asinco-Bowman spectrophotofluorareter . Results 1.

Adrenal Functi on in the Ghroaic Hypert h yroid Rat To assess adrenal function in the chronic hyperthyroid rat, thy-

raodne was injected at a dose of 16 micrograms/100 grams every fourth day, as recommended by Tata (10) ; treated animals were sacrificed two days after the last injection and a control group was sacrificed at the same time .

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THYROXINE ON ADRENALS

Vol, 7, No. 15

The result ; of the experiment, tabulated in Table I reveal that thyroxine admini.ytration in doses not. affecting body weight affects adrenal

T and

weight in the normal rat .

As anticipated from the results

of Wurtman (î) and of ?arker and Noble (h) there is an increase in PNMT concomitant with an increase in adrenal gland weight, the PNMT activity per u.n .it of adrenal weight remaining markedly constant . Thyrnxine administration h .;s a marked effect upon rat serum corticosterone : this presents the possibility that the effect of thyroxine on epinephrine formation is mediated through the adrenal cortex .

However,

it will `~e noted that differences in adrenal weight and PIVMT had levelle3 off at the time the increase in serum corticosterone was most mar keci . 3.

roxine l4dren al :\dminis_tere 3_ Cat aholi é_ doses_ ~_ of Th -F. u-tctinn in Rats__ _.Y._ _ ___. As the effects of "hyperthyroid, i~hysiol~gical" at :d of "toxic,

nharmacoi~~~i.cai" doses o: thyroxine have. often teen contrasted, it seemed zppr~~;iriatP to inquiry: into t5e effect of catabolic doses of thyroo:ine on adrenal PNMI" and on serum corticosterone .

To this end, groups

of rats were injectz<1 daily with doses of 10 and 2pp micrograms of thyroxinn ;'1!)O gm . 8, f, rat-day over a period of fourteen days .

To assess

thyr " ~id function in the absence of the thyroid gland znd the sensitisation ~~C the adrenal resç~onsl~ in thyroidectomized animals two thyroidectomi~ed group " " vere included in the exi~eri~ent . 1" }ie re~~~l t~, é~rese : : : " d in Table II indicate an increase in relative :adrenal 3land ~:.:i3ht at dose :; of 1~~ mi.crograms (P
liven a S microgram dose (P
there via ":, upon rhyro_decto :"y, no relative bu : an absolute decrease in adrenal

T and

weight,

P~n1T activity closely followed adrenal weight ex-

cef~t for a slight increase in PNMT per unit of adrenal weight in the thyroidectomi.~~~d animals given thyroxine .

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THYROXINE ON ADRENALS

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followed the general pattern of rat adrenal PNMl;however, the corticosterone level of the thyroidectomfzed group did not fall below that of the normal group . Summary The preliminary data presented here indicate that the administration of thyroxine to the normal rat results in an increase in adrenal weight, in adrenal PNMT and in serum corticosterone level,

These

affects are largely reversed in the thyroidectomized animal which, in turn, is sensitized to thyroxine .

Since an increase in adrenal epine-

phr.ine has been shown to accompany an increase in PNMT (5)

the possi-

bility exists that thyroxine is zesponsible for an increase in adrenal epinephrine .

The relationship between adrenal PNMT and adrenal epine-

phrine and the relationship between serum corticosterone and adrenal corticosterone production are currently under investigation . References 1.

T . S, HARRISON, Physiol, Rev., 44, 161

2.

M, ZILE and }} . A, LARDY, Arch, Biochem, Biophys .,

3.

I, NDGOESCU et _al in : Current Topics 3n Thyroid Research, Ed . : C . Andreoli, p . 1095 (1965),

4.

H,

5.

R, J, WiR TMAN, Endocrinology-, 79 , 608 (1966),

6.

L, N . PAR KER and E . P, NOBL&, Proc . Soc, F]cp tl ., Biol . Med ., 1~, 734 (1967) .

7.

A, M, BARRSTT and M, A, STOCKHAM, J . Endocrin ,, ~ 97 (1963) .

8.

R . J, WU2TNAN .and J . AXELROD, J . Biol, Chem ., 2~, 2301 (1966),

9.

N, ZENKER and D . E . BF~2NSTEIN, J, Biol . Chem ., 231, 695 (1958),

10 .

(1964),

EARTLY and C . P, LEBLOND, fihdoc rinolo

J, R .

s,

411 (1959),

, ~, 249 (1954) .

TATA et al, Bioçh eau, J ., 86, 408 (1963) .