Action of Growth Hormone and Thyroxine on Aortas of Hypophysectomized Dogs

Abstract

Young dogs were surgically hypophysectomized and maintained for eleven weeks postoperatively with age-matched normal controls. For three weeks prior to sacrifice, four hypophysectomized dogs were given daily injections of bovine growth hormone (GH, 0.2 mg./kg.) and another four were given daily injections of thyroxine (T 4 , 5 /tg-/ kg.). Aortas were removed, cleaned of adventitia and divided into three segments: arch, thoracic and abdominal. Each portion was analyzed for collagen, elastin, deoxyribonucleic acid (DNA), calcium, total mucopolysaccharides (MPS), hyaluronic acid (HA), heparan sulfate (HS), dermatan sulfate (DS) and chondroitin sulfate (GS). The arch and thoracic aortas of normal animals were found to contain more DNA, CS and elastin but less collagen than the abdominal aorta. Removal of the hypophysis resulted in an overall increase in elastin and DNA content and caused a decrease in all sulfated MPS. Administration of either CH or T 4 to hypophysectomized dogs had a profound effect on the majority of constituents in all segments of aorta. CH returned the content of elastin, DS and CS toward normal in at least two of the three aortic segments. T 4 returned the content of DNA, DS and CS toward normal in all segments. Moreover, T 4 treatment caused significant reductions in collagen and HA contents of thoracic and abdominal segments. These results indicate that: (1) the composition of normal aorta varies with the segment studied; (2) the composition of the aorta is markedly affected by hypophysectomy, CH and T 4 treatment; and (3) individual aortic segments show differential sensitivity to a given hormone. DIABETES 22:243-50, April, 1973. of the aortic wall and that replacement therapy with growth hormone (GH) partially corrects the metabolic defects. 1 ' 3 In the present paper we would like to give a more detailed account of the effects of GH than in our preliminary communications, and also to report on the effect of thyroxine (T 4 ), which was studied in our laboratory under comparable conditions. It was found that the action of T 4 on the aortic wall is different from but in some ways supplementary to that of GH. MATERIALS AND METHODSMongrel dogs of either sex between the ages of six and eighteen months and weighing between 8 and 12 kg. were hypophysectomized by the transbuccal technic as described. 4 Previous experiments from this laboratory have shown that little difference exists in the composition of aorta between the ages of six and eighteen months in mongrel dogs of either sex. 5 Completeness of the hypophysectomy was checked by histological examination of the removed tissue and by postmortem examination of the sella turcica. After surgery, dogs remained in the animal colony for eight weeks without hormone treatment. Then, four of the hypophysectomized dogs received subcutaneous injections of a highly purified bovine GH preparation (Wilhelmi, Lot no. 12, gift of the Endocrinology Study Section, N.I.H., Bethesda), 0.2 mg./kg./day for three weeks. Another four of the hypophysectomized dogs r...

Intermittent hyperinsulinaemia and arterial glycosaminoglycans in dogs

“…We have reported previously that various segments of the arterial system show differences in response to disturbances in endocrine homeostasis such as diabetes [11,17], hypophysectomy and replacement therapy with pharmacological doses of a variety of hormones [10,11,16,17]. This differential hormone sensitivity was apparent also in the present series of experiments in both diabetic and hypophysectomized dogs treated with insulin.…”

“…Although all four GAG fractions were measured in eight arterial segments, only the data significantly different (p < 0.01) from hypophysectomized controls are presented. No comparison between normal and hypophysectomized dogs is given, since it is known that hypophysectomy itself significantly lowers the arterial GAG content [10,11,15,16], and this is not a point at issue. The effect of insulin on the GAG distribution in hypophysectomized dogs was not strictly comparable to that seen in diabetic dogs.…”

“…Hypophysectomies were performed by the transbuccal procedure [10,11]. Completeness of the hypophysectomy was checked by histological examination of the removed tissue and by post-mortern examination of the sella turcica.…”

Arterial Glycosaminoglycans in Diabetic Dogs

“…The majority of the experimental work has been done on aortic tissue of small animals and it was tacitly assumed that the results were rep resentative of metabolic properties of the ar terial system in general (12). On the other hand, we have reported that the glycosamino glycan (GAG) content of such diverse vessels as aorta, coronary and renal arteries is by no means uniformly altered in dogs following hypophysectomy and hormonal replacement therapy (2,3,(13)(14)(15). Indeed, marked dif ferences in response were observed even amongst the three aortic segments, the aortic arch being less sensitive to alterations in hor mone homeostasis than were the thoracic and abdominal segments (2).…”

Effect of Hormones on the Glycosaminoglycan Content of Canine Renal Arteries

“…It was previously shown in our laboratory that (a) removal of the hypophysis in the dog reduced the glycosaminoglycan (GAG) content of both aorta and coronary arteries, and (b) replacement therapy with soma totropin (STH), thyroxine, estrogen, progesterone or testosterone was ca pable of raising the GAG content in various aortic segments, but had no significant effect on coronary arteries [2,17,18]. This sort of difference in sensitivity prompted us to study the effect of hormones also on other arteries of the canine vascular tree -in this case the renal arteries.…”