Robert K. Burns

Effects of Hypophyseal Hormones Upon Amblystoma Larvae, Following Transplantation or Injection, With Special Reference to the Gonads.

When the hypophysis of an adult western axolotl is transplanted intact into young larvae of Amblystoma trigrinum, 30-35 mm. in length, the graft usually establishes itself permanently. The results are soon manifested in the following order: (1) the pigmentary system responds by a gradual expansion of the melanophores and an increase in number culminating in sooty blackness; (2) a marked growth stimulation with acromegalic symptoms; (3) a hypertrophic effect upon the immature gonads, which is relatively enormous and occurs without exception in the case of the testis, but is relatively slight and frequently absent in the case of the ovary. There is a tendency to metamorphose earlier than normals reared under identical conditions of environment and nutrition. The pigmentary reaction begins several days after implantation, and first appears as an intensification of the dark areas in the normal pattern. Soon, however, darkening of the lighter areas begins, and in 2 to 3 weeks a uniform blackness of sooty intensity is attained. This effect is attributable to the hormone produced by the pars intermedia, and is well known from the work of many, among whom may be mentioned Smith and Smith, 1 and Allen. 2 The effect upon growth is seen in a tendency to slightly greater length, greater girth, and a conspicuously enlarged head in which the ratio of width to length is noticeably increased. The growth effect and acromegalic condition are attributed to the hyperstimulative action of the pars anterior. This stimulation of growth is, conversely, to be expected from the work of Allen 3 and Smith, 4 both of whom observed retardation of growth following hypophysectomy in frog tadpoles. Also, Evans and Long 5 produced gigantism in rats by administration of an alkaline extract of the mammalian anterior hypophysis.

Thalidomide inhibits UVB-induced mouse keratinocyte apoptosis by both TNF-α-dependent and TNF-α-independent pathways

Background: Thalidomide is an anti‐inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti‐inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor‐alfa (TNF‐α) production by monocytes. However, its mechanism of action in the skin is not known.

Effects of Female Sex Hormones in Young Opossums

Summary Estradiol dipropionate and estrone have only a gynogenic action on the genital tracts of young opossums of either sex, contrasting in this respect with the male hormone testosterone propionate which exerts a dual effect. The most striking effects are exerted on the phallus and the epithelium of the urinogenital sinus. Müllerian ducts, although very immature, are definitely enlarged. Prostatic outgrowths are suppressed.

Hormonal Control of Sex Differentiation

THE knowledge that the gonads exercise some form of remote control over sex structures and characters of all categories is not new. The effects of castration on the animal body have been well known since ancient times. However, it is usual to credit Berthold (1849) with the first experimental demonstration that substances originating in the gonads and distributed with the circulating blood are necessary for the maintenance of structure and function in the reproductive system. Concrete application of the hormone theory to the development of sex is relatively recent, dating from the first satisfactory analysis of the freemartin problem arrived at independently by Lillie, and Keller and Tandler in 1916. This milestone marked at once the end of a problem of long standing and the beginning of a period of experiments on the mechanisms of sex differentiation, differing widely in method but having in common the theoretical conception developed for the freemartin-that sex-specific hormones are produced, circulate with the blood and act upon the appropriate embryonic structures during the plastic stages of development. It is unnecessary now to review the freemartin case, for both facts and argument are well known. However, in arriving at a satisfactory general theory many secondary but nonetheless important questions were developed. Many of these are critical for the further extension of our theoretical structure. We may mention (1) the problem of the nature of the sex-differentiating hormones and their

Effect of Testosterone Propionate on Sex Differentiation in Pouch Young of Opossum

Summary The administration of testosterone propionate to the pouch young of the opossum induces development of a strange medley of the characters of both sexes. On the male side the phallus, wolffian duct, epididymis, rete, and the glands of the urinogenital sinus are all stimulated, and the effect is commonly greater in males than in females. Müllerian duct derivatives are also stimulated, however, but more so in the female. Differentiation of the gonads is not profoundly affected, and scrotum and pouch are entirely unresponsive. For most structures a sex factor apparently affects the degree of the response.

Origin and Differentiation of Epithelium of Urinogenital Sinus in the Opossum

Summary and Conclusions 1. Those epithelia in the urinogenital tract of the opossum which respond to estrogens by squamous metaplasia and cornification, have a common origin from the lining of the urinogenital sinus. 2. The sinus epithelium itself is apparently derived at an early stage of development from the ectodermal cloaca or uro-proctodeum, and perhaps in part from the urethral plate. 3. The primitive cloacal endoderm is eventually restricted to the bladder proper. 4. A common ectodermal origin best explains the histological and physiological likenesses of the tissues involved, and the occurrence of stratified squamous epithelium in the lower urinogenital tract of mammals generally. Early development in higher mammals needs reinvestigation with respect to this point. 5. The use of hormones (particularly estrogens) in the immature organism is a valuable method of precociously differentiating tissues not so readily delimited in normal development of the urinogenital tract.

Development of the Mesonephros in Amblystoma after Early Extirpation of the Duct

The mesonephros in Amblystoma develops from the 9th (or 10th) embryonic somite to the twentieth, at the level of the cloaca. The anterior region, corresponding approximately to segments 10-15, bears the usual relation to the gonad and is the so-called “sexual kidney.” The posterior region, more massive and anatomically more complex (due to the presence of secondary, tertiary units, etc.) is the “secretory kidney.” Both regions develop from a continuous band of nephrogenic tissue, the “mesonephric blastema” dorso-medial to and contiguous with the primitive kidney duct or pronephric duct. Very early in differentiation the mesonephric units of both regions establish connections with this duct, which thus becomes the mesonephric duct. There is, however, a marked delay in the development of the posterior region, during which the units of the sexual kidney are well developed and functional; and it is to this region of delayed development that secondary, tertiary, etc., tubules are confined. These statements rest largely on the early work of Hall. 1 Such differences in morphology, chronology and functional relations raise interesting problems of homology. In view of the early association between the rudimentary mesonephric units of both regions and the duct, it was decided to investigate the result of elimination of the latter upon the origin and differentiation of the former. In Amblystoma the primitive duct (pronephric duct) arises at the level of somites 3 and 4, and gradually grows posteriorly along the ventral border of the row of somites until it reaches the cloaca at the level of somite 20. At stages 26-27, Harrisons Series, the growing end of the duct reaches only to the 8th or the beginning of the 9th somite, and at or prior to this time may be removed without disturbing the mesonephric region.

Transformation of Testis to Ovary in Heteroplastic Parabiosis in Amblystoma

A study of sex reversal in heteroplastic combinations of Amblystoma has been in progress for some time, and a total of 146 pairs of A. tigrinum—A. punctatum have been studied, in which both partners are sexually differentiated. The advantage of heteroplastic combination lies in the more rapid development and larger size of the tigrinum member, which invariably becomes sexually dominant at a relatively early stage, regardless of its own sex. Likewise, the gonads of the punctatum member, irrespective of sex, undergo modification and reversal in varying degree. In the present paper we shall confine ourselves to an outline of the process of transformation from testis to ovary in the gonads of punctatum males joined to large tigrinum females. In accordance with the laws of chance combination, 4 sex-species combinations are possible, and up to about 90 days in the experiment these occur in the expected ratio, as follows: .∗ From this it is apparent that such factors as early mortality, or atypical sex ratios in the eggs used, can be excluded as influencing the result. And since the mortality subsequent to sex differentiation was low, and moreover included in the data, this factor, difficult to rule out in past experiments, is here completely eliminated from the result. In the later stages of the experiment the expected ratio is greatly modified due to complete reversal of sex in the punctatum member of many pairs of the group. This is accompanied by a corresponding excess of pairs: . These data, coupled with the histological evidence to be summarized, force us to conclude that virtually all punctatum males united to large tigrinum females undergo reversal of sex, which is, in many instances, already complete. The histological evidence may be summed up in the following principal points: (1) Histological transformation of testis to ovary is seen in the gonads of almost all punctatum members of pairs prior to 90 days, beyond which few such pairs can be found. The only exceptions are found in a few quite young pairs.

Ovulation in the Neotenic Amblystoma Tigrinum Following Administration of Extract of Mammalian Anterior Hypophysis

Ovulation in adult amphibians has been experimentally induced by hypophyseal transplants or by administration of extracts of the hypophysis in a number of species by various workers. Wolf 1 succeeded in producing ovulation out of season in frogs by means of homoplastic transplantation of anterior hypophysis. Houssay, Giusti, and Lascano-Gonzalez 2 and Houssay and Giusti 3 were able to bring about a similar response in toads by the use of homoplastic implantations of anterior lobe. The results obtained by Noble and Richards 4 on the salamander Eurycea bislineata, in which ovulation has been induced by means of homoplastic transplants, are confirmed by the findings of Adams 5 , 6 who was able to obtain egg-laying in adult Triturus viridescens and Triton cristatus by the same means. Similar results were observed by Adams 7 , 8 if heteroplastic transplants from anurans were substituted for the homoplastic implants. Adams 9 was also able to confirm the earlier findings of Houssay et al on ovulation in toads, in being able to elicit the response only with homoplastic transplants of anterior lobe substance. Ovulation has likewise been produced in anuran amphibians with extracts of the mammalian hypophysis. Through the administration of an alkaline aqueous extract of the anterior lobe of cattle, Kehl 10 induced ovulation in the mature frog, Discoglossus pictus, and Adams 9 using a similar extract obtained the same response in frogs. Up to the present time there appears to be no record of ovulation in urodele amphibians produced by means of extracts of mammalian hypophysis.