Search PubMed⌕ Search

Biomedical subjects

R V Short

Publications and source records attributed to R V Short.

At least 73 records · Page 4Linked to original sources

Sex determination in marsupials: evidence for a marsupial-eutherian dichotomy.

In this paper, we review briefly the current state of knowledge about sexual differentiation in eutherian mammals, and then describe the situation in detail in two marsupial species: the North American opossum and the tammar wallaby. The conventional explanation for the genesis of all male somatic sexual dimorphisms in mammals is that they are a consequence of the systemic action of testicular hormones. In the absence of testes, the embryo will develop a female phenotype. We present evidence for the tammar wallaby that calls into question the universal applicability of this hormonal theory of mammalian sexual differentiation. We have shown that extensive somatic sexual dimorphisms precede by many days the first morphological evidence of testicular formation, which does not occur until around the third day of pouch life. Male foetuses, and pouch young on the day of birth, already have a well-developed gubernaculum and processus vaginalis, paired scrotal anlagen, and a complete absence of mammary anlagen, whereas female foetuses and newborn pouch young have a poorly developed gubernaculum and processus vaginalis, no scrotal anlagen, and well-developed mammary anlagen. Because it seems unlikely that the male gonad could begin hormone secretion until after the Sertoli and Leydig cells are developed, our results strongly suggest that some sexually dimorphic somatic characteristics develop autonomously, depending on their genotype rather than the hormonal environment to which they are exposed. We have been able to confirm the hormonal independence of the scrotum, pouch and mammary gland by administering testosterone propionate daily by mouth to female pouch young from the day of birth; although the Wolffian duct was hyperstimulated, there was no sign of scrotal development, or pouch or mammary inhibition. When male pouch young were treated with oestradiol benzoate in a similar fashion, there was hyperstimulation of the Müllerian duct and inhibition of testicular migration and development, but no sign of scrotal inhibition or pouch or mammary development. Our results in the tammar wallaby are consistent with the earlier studies on the opossum, whose significance was not appreciated at the time. Further evidence in support of this hormonal independence comes from earlier studies of spontaneously occurring intersexes in several species of marsupial, including the opossum and the tammar wallaby. An XXY individual had intra-abdominal testes and complete masculinization of the male reproductive tract internally, but externally there was a pouch and mammary glands and no scrotum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Primary genetic control of somatic sexual differentiation in a mammal.

The classical view of mammalian sexual differentiation is that a gene on the Y chromosome transforms the indifferent gonad into a testis. The Leydig cells then secrete androgen which stimulates the development of the male reproductive tract, and the Sertoli cells secrete Mullerian inhibitory substance which inhibits the development of the female reproductive tract. In the absence of a testis, the Mullerian duct develops into the Fallopian tubes, uterus and vagina. Thus the whole of sexual differentiation is thought to be hormonally mediated as a consequence of this initial genetic determination of gonadal sex. We have found evidence in a marsupial mammal for extensive sexual dimorphisms which precede any morphological differentiation of the gonads. Thus the classical view of mammalian sexual differentiation may have over-emphasized the role of testicular hormones, and overlooked earlier genetic effects.

Animals↗

Müllerian inhibiting substance production and testicular migration and descent in the pouch young of a marsupial.

The ontogeny of Müllerian inhibiting substance (MIS) production by the developing testis of an Australian marsupial, the tammar wallaby (Macropus eugenii), was determined during pouch life using an organ-culture bioassay of mouse fetal urogenital ridge. This information was related to the morphological events during testicular migration and descent. MIS biological activity was found in testes (but not ovaries or liver) of pouch young from 2 to 85 days of age. MIS production had commenced by day 2, which is within a day of the first gross morphological signs of testicular differentiation. Müllerian duct regression occurred between 10 and 30 days, which partly coincided with testicular migration to the inguinal region and enlargement of the gubernacular bulb (15 to 30 days). These observations are consistent with the hypothesis that MIS may be involved in testicular transabdominal migration. The epididymis commenced development and growth only after the testis had descended through the inguinal ring. This provides no support for the suggestion that the epididymis is involved in testicular descent into the scrotum. The basic sequence of events in post-testicular sexual differentiation in the wallaby is sufficiently similar to that seen in eutherian mammals to make it an excellent experimental model for future studies of testicular differentiation, migration and descent.

Animals↗

Experimental manipulation of sexual differentiation in wallaby pouch young treated with exogenous steroids.

We have investigated the effects of androgen or oestrogen treatment of female or male tammar wallabies from the day of birth, when the gonads are histologically undifferentiated, to day 25 of pouch life, when the gonads and the Wolffian and Müllerian ducts have differentiated and the testes have migrated through the inguinal canal. Female tammars treated with testosterone propionate (24-50 mg kg-1 day-1) orally for 25 days had enlarged Wolffian and Müllerian ducts. Mammary and pouch development, however, was indistinguishable from that of control females. The treatment had no apparent effect on ovarian development, or on ovarian position in the abdomen. The phallus of males and females was similar in size, and neither experimental treatment had a significant effect on its size at day 25. Male tammars treated with oestradiol benzoate (1.2-2.5 mg kg-1 day-1) orally for 25 days had gross hypertrophy of the urogenital sinus. Testicular morphology was abnormal; many of the germ cells appeared necrotic, the seminiferous tubules were of reduced diameter, and there were few Leydig cells and increased amounts of fibrous tissue between the tubules. The cortex of these gonads contained some areas which had an ovarian appearance, lacking tubules and containing numerous germ cells. The Müllerian ducts of control males had regressed, but this was prevented by oestrogen treatment, suggesting an inhibition of either Müllerian Inhibiting Substance (MIS) production or its action. Normal testicular migration was inhibited in treated males; the testes remained high in the abdomen, similar in position to the ovaries of control females, whilst control males all had testes in the inguinal region. The gubernaculum and processus vaginalis of control males extended into the scrotum, but in treated males they terminated outside it. Oestrogen treatment had no effect on the size of the scrotum and did not induce mammary or pouch development. These experiments show that marsupials, like eutherians, have a dual hormonal control of Wolffian and Müllerian development. By contrast, the initial development of the mammary glands, pouch, gubernaculum and scrotum does not appear to be under hormonal control and is therefore likely to be autonomous and dependent on genotype.

Animals↗

The correlation between serum and salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates: two non-invasive techniques for monitoring human circadian rhythmicity.

Although there is a circadian rhythm in blood melatonin concentrations in humans, the problems associated with frequent blood collection limit the use of this rhythm in the investigation of the circadian system and in the diagnosis and treatment of chronobiological disorders. Therefore, to establish a convenient, non-invasive technique for monitoring melatonin circadian rhythmicity, we compared the melatonin concentrations in blood samples collected from five subjects every 2-4 h over a 26 h period, with the melatonin concentrations in saliva samples and with the total amount of 6-hydroxymelatonin sulphate excreted in the urine during 2-h periods. There was significant correlation between serum and salivary melatonin concentrations (r = 0.81, P less than 0.001), and between serum melatonin concentrations and 6-hydroxymelatonin sulphate excretion rates (r = 0.72, P less than 0.001). The results demonstrate that both salivary melatonin concentrations and urinary 6-hydroxymelatonin sulphate excretion rates are reliable indices of serum melatonin concentrations. These measurements, in combination with frequent sample collection, provide two convenient, non-invasive techniques for monitoring melatonin circadian rhythmicity.

Adult↗

Hypothalamo-pituitary portal blood concentrations of beta-endorphin during suckling in the ewe.

Matched hypothalamo-pituitary portal and jugular blood samples were collected over about 6 h from 7 lactating Corriedale ewes penned with their lambs, and a careful record was kept of ewe/lamb behaviour. Hypothalamo-pituitary portal blood concentrations of beta-endorphin were measured by radioimmunoassay and the secretion rates were calculated; these were related to peripheral plasma prolactin and LH concentrations, and the sucking bouts of the lambs. Basal LH concentrations remained less than 1 ng/ml with 0-2 pulses of 1.5-3.5 ng/ml amplitude per 6-h collection period. Prolactin secretion was episodic with individual baselines varying from 24 to 286 ng/ml, and peak concentrations of 50-631 ng/ml. Portal beta-endorphin was secreted in an episodic pattern with individual baseline secretion rates varying from 0.125 to 0.495 ng/min, and peak secretion rates of 0.768 to 3.216 ng/min. A close correlation was seen between sucking bouts and the secretion of portal beta-endorphin and peripheral prolactin; 86% of sucking bouts resulted in a significant release of beta-endorphin, and 46% of sucking bouts resulted in a significant release of prolactin. These results show that hypothalamic beta-endorphin is released in response to the sucking stimulus. This provides support for the hypothesis that, during lactation, beta-endorphin acts within the hypothalamus to reduce GnRH release and hence depress pituitary gonadotrophin secretion.

Animals↗

Salivary oestriol and progesterone concentrations in women during late pregnancy, parturition and the puerperium.

Oestriol and progesterone concentrations were measured by specific radioimmunoassays in the saliva of six women on a daily basis during the last month of pregnancy, at frequent intervals during labour and daily during the puerperium. Salivary steroid concentrations are thought to reflect the circulating concentrations of the free hormone, and hence may be more biologically relevant than the total plasma concentration, or the urinary excretion of a metabolite. There was no sign of a fall in salivary oestriol or progesterone concentrations before the onset of labour. During the first and second stages, the concentrations fluctuated widely, perhaps due to alterations in uterine blood flow. After delivery of the placenta, hormone concentrations declined abruptly. Oestriol reached undetectable levels of less than 0.1 nmol/l within a day, whereas progesterone concentrations declined somewhat more slowly, approaching follicular-phase values after 2-3 days. This slower decline in the concentration of progesterone may be due to a leaching-out of the hormone from body fat stores. The absence of any prepartum progesterone withdrawal presumably explains the characteristic postpartum delay in the onset of lactogenesis.

Adult↗

Synchronization of mammalian circadian rhythms by melatonin.

While pinealectomy (Px) has little effect on mammalian circadian rhythms, daily injections of the pineal hormone melatonin in rats have profound effects. These can be classified according to their effects under three categories of desynchronization: external desynchronization, internal desynchronization and phase-shift of the zeitgeber (Aschoff, 1969). Externally desynchronized rats, free-running in constant darkness (DD), can be entrained to a 24-hour regime of melatonin injection. Entrainment depends upon the suprachiasmatic nuclei (SCN) since lesions to the SCN prevent it. Although no animal model for internal desynchronization exists, rats whose circadian rhythms are disrupted or arrhythmic in constant light (LL) are synchronized by daily melatonin injection, and the rate and direction of responses to phase-shift of the zeitgeber can be altered with daily melatonin administration. These and other results suggest melatonin may be useful therapeutically for such human desynchronizations as jet-lag and shiftwork, and preliminary data using human subjects are presented.

Adult↗

Influence of passive immunization against GnRH on pregnancy and parturition in the tammar wallaby, Macropus eugenii.

Pouch young were removed from 10 wallabies in lactational diapause, and half the animals were injected intravenously with 8 ml normal wallaby serum or 8 ml GnRH antiserum every 3rd day from the day of removal of pouch young until Day 30. Laparotomies were performed on Day 24 to monitor luteal size, follicular development and uterine enlargement. The pouches were examined daily for the presence of newborn young from Days 26 to 30, and all the animals were killed on Day 30. The corpora lutea had hypertrophied in all the animals of both groups by Day 24, but none of the antiserum-treated animals showed any signs of follicular development (follicles less than 1 mm diam.), whereas all the control animals had large follicles (mean 3.5 mm diam.). In each group 4/5 animals were visibly pregnant at laparotomy, and parturition occurred normally in 3 of the experimental animals and 1 of the controls. At autopsy, none of the antiserum-treated animals showed any evidence of follicular development or post-partum ovulation, whereas 3 of the controls had new corpora lutea and the other 2 had large preovulatory follicles. These differences were reflected in the weights of the lateral vaginae; the treated animals showed no evidence of oestrogenic stimulation (4.9 +/- 0.2 g), whereas the controls showed the hypertrophy characteristic of oestrus (9.5 +/- 1.2 g). Lactogenesis, as measured by an increase in mammary gland lactose concentrations, was established in all animals, regardless of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Breast feeding.

Explore the source record for details and available documents.

Animals↗

Immunogenetics of sex determination of the polled goat.

Using the protein A rosette technique, it was found that the gene for polledness (P) in goats is associated with the presence of H-Y antigen on the cell surface of cultured fibroblasts. Two XX intersex goats (P/P) were found to be H-Y+, and one heterozygous (P/+) normal XX female was also found to express H-Y antigen at a low level. The expression of H-Y antigen by intersex goats was found to be lower than that of normal XY males. The statistical analysis suggests that animals of the same genotype and sex might differ in the density of H-Y antigen on their cell surface, which might explain the variability in primary sex determination among intersex goats. The association between the gene for sex reversal and H-Y antigen is discussed in relation to the location of the H-Y gene(s).

Animals↗