Effects of ovarian hormones on the bile flow and pancreatic enzyme secretion in the rat
[영문]Since Rock Pincus, and Garcia introduced estrogen-progesterone preparations into the field of fertility control in 1956, this form of therapy has been widely accepted and applied. From the beginning of these experiments, concern about the theoretical disadvantages has stimulated a magnanimous worldwide research effort.
Almost simultaneously it was observed by several groups of workers that oral contraceptives containing both an estrogen and a progesterone might increase hepatic enzyme(G.O.T. and G.P.T) levels and bromsulphthalein retention(Eisalo et al. 1964, Palva and Mustula 1964, Sotaniemi et al. 1964) or might give rise to
intrahepatic cholestatic jaundice (Adlercreutz and Ikonen 1964, Fawcett and Pedersen 1964, Sotaniemi et al. 1964). It was suggested (Adlercreutz and Ikonen 1964) that the jaundiac caused by oral contraceptive might in many cases bear some relationship to intrahepatic cholestatic jaundice of pregnancy. Later observations seem to indicate that these two types of jaundice have a similar etiology; in the case of intrahepatic jaundice of pregnancy the cause seems to be increased sensitivity of the liver to endogenous steroids produced by the fetoplacental unit
(Schaffner 196, Ockner and Davidson 1967, Kappas 1967, Adlercreutz et al. 1967, Kreek et al. 1967a)
Eisalo et al.(1964), Kreek et al. (1967 b), Muellr et al. (1967), amd Gallagher et al. (1966) from their extensive studies have emphasized the importance of the C-18 steroids in reducing the secretory capacity of the liver, which is indicated by impairment of BSP disposal or increase of serum bilirubin without signs hemolysis in certain patients receiving these steroids.
Forker(1969) reported that the large dose of estrone employed in his experiment 1ed to a moderate loss of body weight, an increase in the liver weight and diminished bile flow. He also stated that changes in passive permeability of the canalicular membrane might lead to reduction of bile formation in rats.
On the other hand, Paul (1972) reported that the estrogen treated rats did not show any change of body weight while the control showed a gain in body weight, and that the liver weight was increased in the oophorectomized rats following estrogen
Spellacy(1969) after a review of worldwide literatures described that the estrogens appeared to have an effect on carbohydrate metabolism and that the action of estrogens was dependent upon the type of estrogen, the dosage schedule, and the
carbohydrate status of the individual being treated. He also described that the progestins either did not adversely affect or might possibly improve glucose tolerance.
Many studies have shown that oral contraceptives increase plasma concentration of cholesterol and triglycerides and decrease post-heparin lipolytic activity during treatment with estrogen containing oral contraceptives (Aurell et al. 1966, Wynn et al. 1966, Gershberg et al. 1968, Zorrila et al. 1968. Stokes and Wynn 1971). Otway and Robinson (1968) suggested that a rise in the rate of triglyceride fatty acid input into the blood could result from an increase in the amount of dietary fat ingested, or from an increase in the extent of hepatic lipogenesis leading to a rise in the rate of release of triglyceride fatty acid from the liver.
Present study was undertaken to observe the effects of estrogen-progesterone preparations upon pancreatobiliary excretion and pancreatic enzymes. Female albino rats weighing around 180 gm were employed and divided into six groups, each
comprising 14 to 30 rats. For four consecutive weeks the first group was served as a control, the second group was administered intramusculary 30㎍ per kg weight of estradiol benzoate four times a week. the third group was administered 300㎍ per kg
weight of estradiol benzoate four times a week, the fourth group was administered 5 mg per kg weight of medroxyprogesterone acetate four times a week, the fifth group was oophorectomized and allowed 10 days of recovery period, and the sixth group was
administered 300 ㎍ per kg weight of estradiol benzoate daily on oophorectomized rats.
The results obtained are summarized as follows:
1. In the estradiol treated group the liver weight and the bile flow was increased on the first week and returned to normal control level after the second week. However the bile flow on the large dose of estradiol showed decreasing tendency.
2. The excretion of pancreatic enzymes in the group of estradiol administration showed decreasing tendency. This tendency was more marked in the group of large doase administration.
3. In the group of medroxyprogesterone acetate administration bile flow was reduced on the first week, increased on the second and third week, and returned to normal on the fourth week.
4. In the group of medroxyprogesterone acetate administration the excretion of pancreatic enzymes was increased on the third week and returned to normal on the fourth week.
5. In the oophoretomized group reduction of the liver weight, bile flow, and pancreatic enzymes was observed on the first week, but pancreatic enzyme excretion was increased after second week. Large dose of estradiol administration to the oophorectomized group induced increased liver weight on the first week and showed
similar changes in the pancreatic enzyme excretion with oophorectomized group.
6. Changes of billirubin level were unremarkable with administration of estradiol and medroxy progesterone acetate but bilirubin level was markedly increased in oophorectomized groups.
By these findings it may be concluded that long term administration of ovarian hormones affects the exocrine function of the liver and the pancreas significantly, and that the estrogenic component inhibits the glandular function while the
progesterone component stimulates it.