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Jean D Wilson

Publications and source records attributed to Jean D Wilson.

15 recordsLinked to original sources
PubMed2006

Role of the alternate pathway of dihydrotestosterone formation in virilization of the Wolffian ducts of the tammar wallaby, Macropus eugenii.

Dihydrotestosterone in androgen target tissues is formed under most circumstances by the 5alpha-reduction of testosterone, but an alternate pathway involves the oxidation of androstanediol to dihydrotestosterone. To investigate the mechanism by which androgens virilize the Wolffian ducts in the tammar wallaby, [(3)H]progesterone was incubated with testes from d 10 and 19 pouch young, and radioactivity was recovered in testosterone and androstanediol at both ages. Analysis of the intermediates indicates that androstanediol was formed both from testosterone via 5alpha-reduction and 3alpha-keto reduction and directly from 5alpha-reduced progestogens. 5alpha-Reductase activity was high in minces of mesonephros/epididymis from d 6-21 pouch young. When minces of urogenital tract tissues from d 19 pouch young were incubated with [(3)H]testosterone, [(3)H]dihydrotestosterone, and [(3)H]androstanediol, dihydrotestosterone was the principal androgen formed in the mesonephros/epididymis, urogenital sinus, and urogenital tubercle, whereas androstanediol was the principal androgen formed by the testis. In intact pouch young studied between d 10 and 34, administration of the 5alpha-reductase inhibitor, 17beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5alpha-androstan-3-one, blocked virilization of the Wolffian ducts in males, and administration of androstanediol caused virilization of the Wolffian ducts in females. We conclude that dihydrotestosterone, largely formed in the tissue by the oxidation of androstanediol derived from the testes and also the 5alpha-reduction of testosterone, is responsible for Wolffian duct virilization in this species.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2005

Ontogeny and pathway of formation of 5alpha-androstane-3alpha,17beta-diol in the testes of the immature brushtail possum Trichosurus vulpecula.

The testicular androgen 5alpha;-androstane-3alpha,17beta-diol (androstanediol) mediates virilisation in pouch young of a marsupial, the tammar wallaby, and is the principal androgen formed in immature rodent testes. To chart the pattern of androstanediol formation in another marsupial species, the testes or fragments of testes from brushtail possums (Trichosurus vulpecula) that spanned the age range from early pouch young to mature adults were incubated with (3)H-progesterone and the products were identified by high-performance liquid chromatography. The only 19-carbon steroids identified in pouch young and adult testes were the Delta(4)-3-keto-steroids testosterone and androstenedione. However, androstanediol and another 5alpha-reduced androgen (androsterone) were synthesised by testes from Day 87-200 males and these appeared to be formed from the 5alpha-reduction and 3-keto reduction of testosterone and androstenedione. In the prostate and glans penis of the immature male, (3)H-androstanediol was converted to dihydrotestosterone. We conclude that the timing of androstanediol formation in the possum testis resembles the process in rodents rather than in the tammar wallaby and that any androstanediol in the circulation probably acts in target tissues via conversion to dihydrotestosterone.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Steroid 5alpha-reductase 1 promotes 5alpha-androstane-3alpha,17beta-diol synthesis in immature mouse testes by two pathways.

5alpha-Androstane-3alpha,17beta-diol (androstanediol) is the predominant androgen in immature mouse testes, and studies were designed to investigate its pathway of synthesis, the steroid 5alpha-reductase isoenzyme involved in its formation, and whether testicular androstanediol is formed in embryonic mouse testes at the time of male phenotypic development. In 24-26-day-old immature testes, androstanediol is formed by two pathways; the predominant one involves testosterone --> dihydrotestosterone --> androstanediol, and a second utilizes the pathway progesterone --> 5alpha-dihydroprogesterone --> 5alpha-pregnane-3alpha-ol-20-one --> 5alpha-pregnane-3alpha,17alpha-diol-20-one --> androsterone --> androstanediol. Formation of androstanediol was normal in testes from mice deficient in steroid 5alpha-reductase 2 but absent in testes from mice deficient in steroid 5alpha-reductase 1, indicating that isoenzyme 2 is not expressed in day 24-26 testes. The fact that androstenedione and testosterone were the only androgens identified after incubation of day 16 and 17 embryonic testes with [3H]progesterone implies that androstanediol formation in the testis plays no role in male phenotypic differentiation in the mouse.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2004

Penile development is initiated in the tammar wallaby pouch young during the period when 5alpha-androstane-3alpha,17beta-diol is secreted by the testes.

Virilization of the urogenital tract is under the control of testicular androgens in all mammals. In tammar young, prostate differentiation begins between d 20 and d 40 under the control of the testicular androgen 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol), but uncertainties exist about the control of penile development. We performed longitudinal studies up to d 150 of pouch life to define normal penile development and the effects of androgen administration and castration. In control animals the male phallus was longer than the female phallus by d 48. Closure of the urethra in males begins around d 60 and continues to at least d 150. Administration of supraphysiological doses of testosterone to females caused penile development equivalent to that of the male and also induced partial closure of the urethral groove by d 150. Castration of male pouch young at d 25 prevented penile development, whereas the penis in males castrated at d 40, 80, or 120 had partial closure of the urethral groove. Administration of 5alpha-adiol to females from d 20-40 also caused partial closure of the urethral groove and some growth of the phallus at d 150, whereas 5alpha-adiol treatment from d 40-80 or 80-120 caused some penile growth but had little effect on urethral development. These findings, together with the fact that we found no sex differences in plasma levels of testosterone, dihydrotestosterone, 5alpha-adiol, dehydroepiandrosterone, or androstenedione from d 51-227, clearly indicate that the action of 5alpha-adiol between d 20 and 40 imprints later differentiation of the male penis.

Androgens↗
PubMed2004

Blasts from the past.

With this issue of the JCI, we celebrate the 80th anniversary of the Journal. While 80 years is not a century, we still feel it is important to honor what the JCI has meant to the biomedical research community for 8 decades. To illustrate why the JCI is the leading general-interest translational research journal edited by and for biomedical researchers, we have asked former JCI editors-in-chief to reflect on some of the major scientific advances reported in the pages of the Journal during their tenures.

Animals↗
PubMed2003

Unsolved problems in male physiology: studies in a marsupial.

Testicular androgens induce formation of the male urogenital tract in all mammals. In marsupials male development occurs after birth and over a prolonged period. For example, in the tammar wallaby virilization of the Wolffian ducts begins by day 20, prostate formation begins about day 25, and phallic development starts after day 80 of pouch life. Between days 20 and 40 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol) is formed in tammar testes and secreted into plasma. Administration of 5alpha-adiol to pouch young females induces urogenital sinus virilization by day 40 and formation of a mature male prostate and phallus by day 150. 5alpha-Adiol is synthesized in pouch young testes by two pathways, one involving testosterone and dihydrotestosterone and the other 5alpha-pregnane-3alpha,17alpha-diol-20-one and androsterone as intermediates, both utilizing steroid 5alpha-reductase. In target tissues 5alpha-adiol acts via the androgen receptor after conversion to dihydrotestosterone but may have other actions as well. Whether 5alpha-adiol plays a role in male development in placental mammals is uncertain.

Androgens↗
PubMed2003

5alpha-androstane-3alpha,17beta-diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha-pregnane-3alpha,17alpha-diol-20-one as a key intermediate.

The synthetic pathway by which 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol) is formed in the testes of tammar wallaby pouch young was investigated by incubating testes from d 20-40 males with various radioactive precursors and analyzing the metabolites by thin-layer chromatography and HPLC. [(3)H]Progesterone was converted to 17-hydroxyprogesterone, which was converted to 5alpha-adiol by two pathways: One involves the formation of testosterone and dihydrotestosterone as intermediates, and the other involves formation of 5alpha-pregnane-3alpha,17alpha-diol-20-one (5alpha-pdiol) and androsterone as intermediates. Formation of 5alpha-adiol from both [(3)H]testosterone and [(3)H]progesterone was blocked by the 5alpha-reductase inhibitor 4MA. The addition of nonradioactive 5alpha-pdiol blocked the conversion of [(3)H]progesterone to 5alpha-adiol, and [(3)H]5alpha-pdiol was efficiently converted to androsterone and 5alpha-adiol. We conclude that expression of steroid 5alpha-reductase in the developing wallaby testes allows formation of 5alpha-reduced androgens by a pathway that does not involve testosterone as an intermediate.

Age Factors↗
PubMed2002

Androgen physiology: unsolved problems at the millennium.

Androgen physiology differs from that of other steroid hormones in two major regards. First, testosterone, the predominant circulating testicular androgen, is both an active hormone and a prohormone for the formation of a more active androgen, the 5alpha-reduced steroid dihydrotestosterone. Genetic evidence indicates that testosterone and dihydrotestosterone work via a common intracellular receptor, and studies involving in vitro reporter gene assays and intact mice in which both steroid 5alpha-reductase isoenzymes have been disrupted by homologous recombination indicate that dihydrotestosterone acts during embryonic life to amplify hormonal signals that can be mediated by testosterone at higher concentrations. However, in post-embryonic life dihydrotestosterone plays unique roles that have not been elucidated. Studies of other 5alpha-reduced steroids, including the plant hormone brassinolide, the hog pheromones androstanol and androstenol, and 5alpha-dihydroprogesterone (in horses and elephants) indicate that this reaction serves different functions in different systems. Second, during embryonic life androgen causes the formation of the male urogenital tract and hence is responsible for development of the tissues that serve as the major sites of androgen action in postnatal life. It has been generally assumed that androgens virilize the male fetus by the same mechanisms as in the adult, namely by the conversion of circulating testosterone to dihydrotestosterone in target tissues. However, in marsupial mammals there is no sexual dimorphism in the levels of testosterone or dihydrotestosterone at the time the male phenotype forms, and in the pouch young of one marsupial, the tammar wallaby, the testes secrete another 5alpha-reduced steroid, 5alpha-androstane-3alpha, 17beta-diol (5alpha-adiol), into plasma. The administration of 5alpha-adiol to female pouch young causes profound virilization of the urogenital sinus and external genitalia, but within target tissues 5alpha-adiol appears to work after oxidation to dihydrotestosterone. Thus, two separate mechanisms evolved for the formation of dihydrotestosterone in target tissues. 5alpha-adiol is the predominant androgen in neonatal testes in several placental mammals, but it is unclear whether it plays a similar role in other mammalian species.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2002

A double life: academic physician and androgen physiologist.

My work in physiology was designed to investigate the process of androgen action within target cells and to use this information to provide insight into the clinical disorders of androgen action. The discovery that the circulating male androgen testosterone is 5alpha-reduced to a more potent hormone, dihydrotestosterone, in target tissues and that dihydrotestosterone and testosterone work by binding to the same androgen receptor protein has provided insight into the inherited syndromes of androgen resistance that impair the formation of the male urogenital tract during embryogenesis and into the role of continued dihydrotestosterone formation in the pathogenesis of prostatic hyperplasia in dogs and men.

Androgens↗
PubMed2002

The marsupial model for male phenotypic development.

In all mammals, androgen formed in the developing testes is responsible for the aspects of male development in which the Wolffian ducts, urogenital sinus and urogenital tubercle are transformed into the epididymis/vas deferens, prostate and penis. That these events take place after birth in the marsupial makes it possible to examine male phenotypic development during pouch life. In the tammar wallaby, Macropus eugenii, the testicular androgen 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha-adiol) is formed in the developing testis, is secreted into plasma and has the capacity to virilize female young pouch when administered exogenously. 5 alpha-Adiol is formed by immature testes in many species and appears to act in target tissues once it has been converted to dihydrotestosterone.

Animals↗
PubMed2002

Administration of 5alpha-androstane-3alpha,17beta-diol to female tammar wallaby pouch young causes development of a mature prostate and male urethra.

Secretion of 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol) by the testes of the tammar wallaby is responsible for initiation of prostatic development after d 20 in male pouch young. To ascertain the role of this hormone in the subsequent growth and differentiation of the prostate and in the development of the male phallus, 5alpha-adiol was administered to tammar female pouch young in two regimens. Administration of the hormone by mouth (8 microg/g body weight.wk) between d 70 and 150 of pouch life caused prostate development equivalent to that in d 150 males and promoted growth and differentiation of the penis, but not masculinization of the urethra. Treatment with a small dose of 5alpha-adiol enanthate (1 microg/g body weight.wk) from d 20-150 produced similar results. However, administration of larger doses of 5alpha-adiol enanthate (10 or 100 microg/g body weight.wk) from d 20-150 caused supraphysiological growth of the prostate, development of a male-type urethra, and penile growth. These results indicate that prostatic development and penile growth can be initiated over a wide time period, but that formation of a male urethra requires androgen action before d 70, when male penile differentiation begins. This further strengthens the hypothesis that 5alpha-adiol is the circulating androgen responsible in this species for virilization during development.

Aging↗
PubMed2002

The hormonal control of sexual development.

The formation of the testis or ovary is a critical step in development. The pioneering studies of Professor Alfred Jost showed that the hormones produced by the embryonic rabbit testis are essential for development of the male phenotype. Sexually dimorphic hormones play a key role in the transition from an undifferentiated gonad into the mature testis and ovary. Marsupials, with their altricial young, provide an accessible model for the study of sexual differentiation because most of these events occur postnatally, while the young are attached to teats within their mothers' pouches. The relatively long time-course for the marsupial sexual differentiation has provided an excellent opportunity to correlate morphological changes with the genes and hormones that control them. Using this model species we have demonstrated that not all sexual dimorphisms are controlled by hormones. Virilization of the prostate and phallus is androgen dependent but appears to rely on circulating 5alpha-androstane-3alpha, 17beta-diol which is converted to dihydrotestosterone in these target tissues. Collectively these studies have led to the development of new paradigms to explain the hormonal mechanisms mediating sexual differentiation.

Animals↗