Effects of fasting and of ACTH on renal compensatory hypertrophy in the 48 hour uninephrectomized rat]

Renal compensatory hypertrophy (R.C.H.) is determined 48 h. after uninephrectomy in fed and fasting rats having free access to a NaCl solution. ACTH (18 gamma/100 g BW/d/2d) enhances R.C.H. in the fed animals. R.C.H. is severely impaired by food deprivation and the remaining kidney looses weight; a normal kidney weight can be maintained if the fasted, uninephrectomized rat is treated with ACTH. These experiments suggest that the stimulation of the adrenal cortex by ACTH has a renotrophic effect. This action may be related to the elevation of blood glucose or/and to the fall of the concentration of plasma K+.     

Influence of nutritional state on lipoprotein lipase activities in the hypothyroid rat

We have investigated the effects of nutritional state on the lipoprotein lipase activities of the experimentally hypothyroid rat. Both short-term effects (i.e., those of a 24 h fast with and without re-feeding) and long-term effects (due to decreased food intake in hypothyroidism) have been studied. The hypothyroid rats had significantly higher lipoprotein lipase activities of adipose tissue and heart muscle. The effect of hypothyroidism on adipose tissue lipoprotein lipase activities was modified by the nutritional state. In rats studied after 24 h fasting, the hypothyroid group had significantly higher lipoprotein lipase activities than weight-matched, age-matched and pair-fed (i.e., semi-starved) control groups. In rats studied in the re-fed state, the effects of hypothyroidism as such were less evident, since the pair-fed group also demonstrated significantly higher enzyme activities than did the other control groups. We have also studied the lipoprotein lipase activities of different enzyme preparations from adipose tissue. The effects of hypothyroidism were most clearly reflected in an increase of heparin-elutable enzyme activity from adipose tissue, whereas adipocyte lipoprotein lipase activity and the lipoprotein lipase secretion rate from adipocytes were affected to a lesser extent. We conclude that alterations in food intake strongly influence the lipoprotein lipase activities in the hypothyroidism. Our data also imply that the increased lipoprotein lipase activity in the hypothyroid state is due to a decreased degradation of the enzyme, both intra- and extracellularly.     

Effect of neonatally injected ACTH and ACTH analogues on eye-opening of the rat.

Three-day old rats were injected subcutaneously either with natural purified pig ACTH (ACTH 1–39), ACTH 1–24, or ACTH analogues as long-acting zinc-phosphate preparations. ACTH 1–39, ACTH 1–24, ACTH 1–18, ACTH 1–16 accelerated the time of eye-opening, whereas an extract of corticosteroids produced $\text{in}$$\text{vitro}$ by excised adrenals of ACTH-treated three-day old rats was ineffective. Injections with ACTH on the twelfth day of life had no effect on eye-opening. It is concluded that a neonatal injection with ACTH or closely related analogues with markedly less corticotropic activity can accelerate the time of eye-opening. This effect is not mediated by the adrenal cortex. The sensitive period for it appears to be shortly after birth.     

Lipoprotein lipase in rat heart--II. Influence of apolipoproteins and nutritional factors on tri-, di- and monoacylglycerol lipase activities in post-heparin effluents

1. The in vitro effects of serum and apolipoproteins (apo), and the influence of the nutritional state of the animals were compared on triacylglycerol lipase (TAGL), diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) activities in post-heparin effluent from rat heart. 2. Serum and apoC-II stimulated DAGL and MAGL 3-fold less than TAGL, the activity that measures lipoprotein lipase (LPL). 3. The preexisting nutritional state of the heart, that strongly modulated LPL, did not influence DAGL and MAGL. 4. ApoA-I, apoC-I, apoC-III1 and apoC-III2 did not stimulate LPL and counteracted its stimulation by apoC-II; MAGL, and not DAGL, was inhibited by apoA-I and apoC-I, an effect reversed by apoC-II. 5. TAGL, DAGL and MAGL appeared to act as a single physiological unit, although differing in functional details; MAGL displayed the greatest dissimilarity.     

Thyroid hormone action on ACTH secretion

Thyroid hormone effects on pituitary ACTH have not been well established. Adult male Sprague-Dawley rats were rendered hypo- and hyperthyroid while undergoing treatment with 6-Propylthiouracil (PTU) and L-Thyroxine (T4). At the time of decapitation, plasma values for T4 (micrograms/100 ml) were 3.9 +/- 0.4 in the control, 17.3 +/- 2.2 in the T4 and less than 2 in the PTU treated group; plasma T3 and TSH confirmed hyper- and hypothyroidism in the T4 and PTU treated groups respectively. Plasma immunoassayable ACTH and corticosterone were significantly increased in hyperthyroid and decreased in the PTU treated animals. Pituitaries were removed and incubated in DMEM. After 3 h incubation, ACTH content and secretion to the medium were significantly lower in the PTU group. As expected, pituitary TSH content and secretion were decreased in the T4 treated animals. These data indicate that thyroid hormones influence pituitary-adrenal function by increasing ACTH secretion and consequently corticosterone production.     

Influence of nutritional factors on the protease production by Leuconostoc oenos from wine

Leuconostoc oenos X₂L isolated from wine secretes two proteases (I and II) into the medium. Growth and protease production were found to be dependent on the composition of the medium. Both proteases were subject to control by ammonium ions and amino acids that repressed their production and the effectiveness was higher on the enzyme II synthesized at the end of bacterial growth. The enzymes were also differently affected by the inclusion of sodium phosphate in the basal medium.     

Studies on the mechanism of action of ACTH on triglyceride synthesis in fat cells.

It was found that ACTH greatly reduced lipogenesis in fat cells in the presence of calcium ion, but not in the absence of calcium ion. Of the enzymes involved in triglyceride synthesis from fatty acid in lipid micelle membranes, only acyl-CoA synthetase was inhibited by calcium ion, the apparent Ki value of calcium ion being 4.2 X 10(-4) M. The Km values of the enzyme for palmitate and ATP were 2.0 X 10(-4) M and 2.5 X 10(-4) M, respectively and calcium ion caused non-competitive inhibition with both palmitate and ATP. The acyl-CoA synthetase activity of lipid micelle membranes was inhibited by treatment with phospholipase A or C, but not by treatment with phospholipase D. The mechanism of inhibition of triglyceride synthesis by ACTH is discussed on the basis of these results.     

Influence of ACTH on serum hormone content and its anticonvulsant action towards infantile spasms

Ten patients with infantile spasms were treated with ACTH, which resulted in a suppression of thyroxine through an increase of the serum cortisol level and suppression of pituitary TSH secretion. The thyroxine level in the excellent-response group was suppressed more than that in the other groups. There was a statistically significant difference (t-test, p < 0.01) in the suppression of T₄ between the excellent-response group and the others. Although the high cortisol level was essential for the clinical effectiveness of ACTH therapy and the suppression of the thyroid hormones, the therapeutic correlation with the elevated cortisol level might be weak as compared to that with the suppression of T₄. These findings suggest the possibility that the efficacy of ACTH therapy in infantile spasms may depend in part on the suppression of the thyroid hormone.     

Biochemical factors involved in the FSH action on amino acid transport in immature rat testes.

Testes of 15-day-old rats preincubated and incubated during different times with various doses of FSH (0.2; 2.0 and 20.0 mU/ml) in Krebs-Ringer bicarbonate (KRb) buffer increase the uptake of [14C] methylaminoisobutyric acid and [14C] aminoisobutyric acid. The basal and FSH stimulated amino acid transport occurs at absolute lower levels when the protein or glycoprotein synthesis is inhibited by cycloheximide (350 mumol/l) or tunicamycin (12 mumol/l) or when the microtubules are depolymerized with colchicine (1.2 mumol/l). However, the proportional increase of amino acid transport produced by FSH was maintained. The blockage of the voltage-dependent Ca++ channels with verapamil or the competitive inhibition of the bivalent ion channels by Co++ or Ni++ nullified the stimulatory action of FSH on the amino acid transport. Also quinine, that blocks the ATP dependent K+ channels, abolished the FSH action. It was concluded that in immature rat testes FSH stimulates amino acid transport through a mechanism involving voltage-dependent Ca++ channels and ATP-sensitive K+ channel.     

Pituitary ACTH responsiveness in the vasopressin deficient rat.

ACTH concentration and the responsiveness of dispersed anterior pituitary cells to hypothalamic extract and to vasopressin were studied in homozygous (DI), heterozygous (HTZ), DI-pitressin treated (DIP) Brattleboro rats, and in control Long-Evans rats.Absolute, but not relative, anterior pituitary weights of HTZ, DI, and DIP animals were significantly smaller than those of controls. The concentration of immunoreactive (I) and bioreactive (B) ACTH in dispersed anterior pituitary cells was greater in DI and DIP than in HTZ or in control animals, although the total amount of ACTH was greater in control than DI or HTZ animals. Media from incubates of pituitary cells derived from DI and DIP animals contained less I and B ACTH than those from HTZ or control animals. Pituitary cells derived from DI animals secreted markedly less ACTH following incubation with hypothalamic extract (NIH-HE-RP-1) than did cells from HTZ animals. The response in DIP animals was intermediate between that of DI and HTZ animals. In contrast, pituitary cells derived from DI and DIP animals were significantly more responsive to vasopressin than those from control or HTZ animals.     

Prostaglandin modulation of the mechanism of ACTH action in the human adrenal.

PGE₁ and PGE₂ significantly increased human adrenal cAMP levels $\text{in}$$\text{vitro}$; cortisol output was also increased in a dose related fashion. In contrast, PGF_1a and PGF_2a depressed adrenal cAMP (except PGF_2a at 100 μg/ml). PGF_1a and PGF_2a depressed cortisol levels at all doses. Indomethacin or 7-oxa-13-prostynoic acid did not affect these parameters. However, when applied in conjunction with ACTH they inhibited or enhanced hormonal action depending upon the temporal sequence of application. The findings indicate that prostaglandins modulate ACTH-adrenocortical cell interaction bidirectionally, initially potentiating and subsequently depressing ACTH stimulated events.