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A. S. PARKES

Detailed precipitin studies have been made of the antigenic properties of thyroglobulin, but some of the results have been criticized on the grounds of lack of purity of the thyroglobulin employed [Hektoen & Schulhof, 1923; Lerman, 1940; Stokinger & Heidelberger, 1937]. The physiological investigation of antithyroglobulin sera, which might throw light on the problem, has been much less pursued. The early results of Rogers & Beebe [1908] suggested that animals could be passively immunized against exogenous thyroglobulin, but several later investigators failed to obtain positive results [Schulhof, 1930; Rosen & Marine, 1937]. Recently, however, Lerman [1941, 1942] has claimed that antithyroglobulin sera will not only immunize against exogenous thyroglobulin, but will also inhibit the action of endogenous thyroglobulin and ultimately lead to a condition of myxoedema. The substance is organ specific rather than species specific, so that antiserum to thyroglobulin obtained from one species will inhibit the activity of that

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A. S. PARKES

A recent study of artificially iodinated proteins showed that biological activity, in relation to acid-insoluble iodine content, was very low compared with that of dried thyroid gland [Deanesly & Parkes, 1945b]. Since the main active principle (thyroxine) is the same in both types of preparation [Ludwig & von Mutzenbecher, 1939] it was concluded that the artificially iodinated proteins at present available contain relatively large amounts of iodine-containing substances which are acidinsoluble but have little or no biological activity. In the case of thyroid preparations it is usually supposed that all the acid-insoluble iodine is thyroxine-iodine and dried thyroid powder is assayed by the chemical estimation of acid-insoluble iodine. Even in thyroid powders, however, some investigators have not found a very close relation between acid-insoluble iodine and biological activity. Thus, Gaddum & Hetherington [1931] concluded that the acid-insoluble iodine content of dried thyroid preparations did not give a reliable indication

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A. S. PARKES

SUMMARY

1. Autografts and intra- and inter-strain homografts of ovarian tissue were made among rats of the two strains, albino and hooded, maintained at the National Institute for Medical Research.

2. Young adult females were ovariectomized and ovarian tissue transplanted subcutaneously. Surviving animals were killed 12–13 months after operation and the grafts, where present, removed for histological examination.

3. The occurrence of vaginal cornification was taken to indicate functional activity on the part of the graft. The effectiveness of the type of graft was assessed by the proportion of 'takes' within a group, by the average latent interval before the appearance of vaginal cornification and by the functional survival time of the graft.

4. The proportion of 'takes' was maximal in the autografts and intra-strain homografts, and only slightly less (16/20) in the inter-strain homografts. The length of the latent interval was not significantly different with the six types of graft. After 12–13 months, when the animals were killed, all the autografts, 11/14 of the intra-strain homografts, and 7/18 of the inter-strain homografts were still functioning. Of the thirty-six homografts which became established sufficiently to cause vaginal cornification, nine failed during the 1st month and three only during the 2nd and 3rd months. There were no later failures.

5. Histologically, most of the grafts were characterized by large follicular or lutein cysts, but normal eggs, follicles and corpora lutea were found in grafts of each type. There was a close connexion between the occurrence of follicular cysts and of persistent vaginal cornification.

6. The comparative importance of immunological and endocrinological factors in the evolution of the ovarian homograft is discussed.

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A. S. PARKES

SUMMARY

Viability of rat ovarian tissue frozen and thawed in vitro was assessed by its capacity to form an endocrinologically active autograft, and variables associated with the treatment have been studied.

Other neutral solutes tested were not as effective as glycerol in protecting against freezing damage, and 15% (v/v) glycerol was more effective than 10% and much more effective than 5%.

The duration of soaking before slow freezing can be reduced with advantage from 1 hr to 15 min.

One-stage rapid freezing to −79° C was very damaging to the tissue as compared with slow freezing, but two-stage rapid freezing, recently described as being effective with bull spermatozoa, gave intermediate results.

Tissue frozen in glycerol-saline deteriorates rapidly after thawing if left at room temperature, but transference to glycerol horse serum after thawing largely preserves viability. Some implications of this result are discussed.

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A. S. PARKES

Folley & Malpress [1944] and Hammond & Day [1944] have recently described the use of the tablet implantation technique for the prolonged administration of oestrogens to cattle. This work, which was carried out in connexion with extensive experiments on the induction of lactation in sterile heifers, raised certain new problems relative to the technique. Chief among these problems were the following.

(a) The large-scale production of the tablets one by one in a hand-operated tablet-making machine proved impossibly laborious. The use of a commercial mechanically operated machine, however, requires that the powder to be tableted shall have certain physical properties, which are usually obtained by the addition of a diluent such as lactose, and a process of granulation. The necessary properties are not possessed by the undiluted microcrystalline oestrogen powders, and the commercial machines are used only with difficulty for such material. The use of tablets containing lactose as a

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A. S. PARKES

The subcutaneous implantation of compressed tablets of pure crystalline material has proved a highly successful method of administering steroid hormones. The essential feature of the technique, which was introduced by Deanesly & Parkes [1937], and which has given particularly favourable results with oestrone, oestradiol, progesterone, testosterone and desoxycorticosterone, is that it allows a very prolonged action for periods up to years from a single administration, and a very high effectiveness in relation to the total dose. The fact that months or years may be required for the complete absorption of a tablet depends on the low solubility of the steroid substances in body fluids, and it would be expected that the existing technique could be applied only to substances of this kind. However, attempts have recently been made to adapt the implantation technique to the administration of a variety of other substances, some of them having a much greater solubility

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A. S. PARKES

The discovery of the gonadotrophic hormones prompted the hope that it would readily be possible to induce fertility in immature or anoestrous animals and to augment fertility in those already capable of breeding. Unfortunately, many difficulties have been experienced, owing to the complexity of the endocrine control of the fertile cycle, to the mixture of effects produced by most of the gonadotrophic preparations available, and to the uncertainty of the extent to which the animal's own pituitary becomes involved. Moreover, the augmentation of fertility in breeding animals presents special problems of a mechanical and metabolic nature.

Early in the work with pituitary hormones, Smith & Engle [1927] reported that they had been able to secure the ovulation of twenty to forty-eight follicles in one ovary of the rat or mouse, and later Engle found [1927, 1931] between.nineteen and twenty-nine implantations at the 9th–10th day of pregnancy. In a later study

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A. S. PARKES

The well-known response of the breast feathers of the Brown Leghorn capon to oestrogens can readily be used to determine the rate of absorption of different esters [Parkes, 1937]. In the male the breast feathers are black; injection of oestrogen while feathers are growing causes deposition of the fawn pigment characteristic of the female. Only that part of the feather is changed which is growing when oestrogen is present; existing plumage is not affected. Since the rate of feather growth is known, the width of the fawn bar in the black feather indicates the time during which effective amounts of oestrogen were circulating. Thus, if a single injection is given, the duration of effect of a compound can easily be ascertained.

In the work previously recorded the duration of action of the following substances was examined: oestrone, oestrone acetate, oestrone benzoate, oestrone methyl ether, oestradiol, oestradiol diacetate, oestradiol monobenzoate, oestradiol

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S. ZUCKERMAN and A. S. PARKES

Testosterone is being widely and successfully used in the clinical treatment of hypogonadal conditions in man [e.g. Hamilton, 1937 a, b; Foss, 1937; Miller, Hubert, and Hamilton, 1938; McCullagh, 1939]. It stimulates the development of the external genitalia and of a masculine distribution of hair; it also heightens the general masculine appearance of the body and face, gives a masculine character to the voice, and induces the mental and behavioural characteristics normal to men. These clinical observations provide more detailed experimental knowledge about the control of secondary sexual characters than is possessed for any other mammal. Very little, for example, is recorded about the endocrine control of secondary sexual characters in sub-human primates. The only observations on the subject of which we know are: (a) that the conspicuous cape of hair of the male Hamadryas baboon (Papio hamadryas) disappears and the pelage changes to the female type after castration [Antonius,

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M Bendayan and I-S Park

Abstract

The existence of extrapancreatic islets in the duodenal mucosa of the adult rat has been established by morphological studies and the development of these islets has been followed from the early embryonic stage to neonatal and adult life. Like the pancreatic islets, glucagon cells were the first to appear at day 12 of gestation. However, in contrast to the pancreatic islets, insulin was not detected in the extrapancreatic islets until birth. At this stage, the different endocrine cells assume their classical topography, insulin cells being surrounded by non-insulin endocrine cells. In addition, the behaviour of these extrapancreatic islets in diabetic conditions was evaluated on streptozotocin-induced diabetic rats as well as on spontaneous BB Wistar diabetic rats. In both conditions, the extrapancreatic islets were found in the duodenal mucosa but were mainly composed of glucagon cells, the insulin cells having disappeared. These results demonstrate that the extrapancreatic islets are a common normal feature of the rat duodenal mucosa. They appear during fetal development, are present in different strains of rats and behave similarly to the pancreatic islets under spontaneous or chemically induced diabetic conditions. Although their exact role remains to be established, they probably react to local hyperglycaemic environment due to intestinal absorption.

Journal of Endocrinology (1997) 153, 73–80