This thesis investigates the age - related decline in the various available measures and estimates of serum testosterone levels in men. Testosterone circulates predominantly bound with high affinity to sex - hormone binging globulin ( SHBG ) in plasma ( ~ 60 % ) and with lower affinity to albumin ( < 40 % ) ; approximately 1 - 2 % circulates unbound in plasma. It is the albumin - bound and free fractions ( termed " bioavailable testosterone " ) that are most likely to have biological effects on target tissues. This thesis reports the establishment, validation and derivation of normal ranges for an ammonium sulphate precipitation method for the measurement of bioavailable testosterone in serum. This method is in use by a number of laboratories at present including the laboratory of Professor John Morley at St Louis University with whom we collaborated. Testosterone has been shown, both cross - sectionally and longitudinally, to decline progressively beginning around the age of thirty. Total testosterone declines at approximately 0.4 % per year while bioavailable and free testosterone decline at approximately 1.2 % per year. The mechanisms that may be responsible for this include age - related changes to the hypothalamic - pituitary - testicular axis, increased SHBG levels, environmental factors, medication and chronic illness. This decline may contribute to a multitude of physiological, psychosexual and cognitive changes associated with ageing in men. This thesis crosssectionally examines the possible determinants of the various fractions of serum testosterone and the associations with various physical, psychosexual and lifestyle variables and with chronic disease and medication use. These cross - sectional data were generated from the Florey Adelaide Male Ageing study, which randomly recruited 568 men from the north and west suburbs of Adelaide, between August 2001 and August 2002. Moreover, this thesis includes a randomised controlled trial of testosterone replacement therapy in men aged 60 years and over with low - normal testosterone levels at baseline, recruited by newspaper advertisement. The goals of testosterone replacement therapy might be to prevent osteoporosis, age related frailty and falls, and to maintain optimal physical, sexual, emotional and cognitive health during the ageing process. This intervention study focused on the effect of treatment on body composition and muscle strength, symptoms of testosterone deficiency, visuospatial cognition, mood, wellbeing and quality of life. Finally, preliminary work was initiated to develop an in vitro bioassay for the measurement of serum testosterone bio - action. This was done using a transient transfection protocol in cultured cells, where androgen receptor and androgen response elements were introduced into the cells, subsequently treated with testosterone containing media and the amplitude of response quantified using a dual - luciferasereporter assay. In summary, this thesis discusses the issues with the measurement of testosterone in plasma and the factors that determine the concentration of the various fractions of testosterone in plasma. A cross - sectional study, using random recruitment procedures was used to investigate associations between testosterone levels and health - related - factors and finally a randomised - controlled - trial of testosterone replacement in ageing men with low - normal testosterone levels is reported. Throughout the thesis, the following themes are common ; body composition, physical function and strength, sexual function, lower urinary tract symptoms and the prostate, visuospatial cognition, mood, quality - of - life and wellbeing. / Thesis (Ph.D.)--Medical School, 2005.

Previous studies of non-human animals and humans with endocrine abnormalities have demonstrated that higher prenatal androgen levels promote more male-typical behavior, including cognitive abilities and sexual behavior. Research on normal hormonal fluctuations (e.g. menstrual cycle studies) has shown additional effects of circulating sex hormones in postnatal life on the expression of a number of sex-linked cognitive and sexual behaviors. This research was designed to replicate previously reported sex differences in a variety of domains and to extend prior findings of an association between low (male-typical) 2nd to 4th digit (2D:4D) ratio, enhanced (maletypical) mental rotation ability, and more liberal (male-typical) sexual attitudes and behavior in women. This is also the first study to examine the effects of hormonal factors and other sex-linked variables on sociosexuality in men. As part of this study, participants (n = 127) completed a battery of gender role measures, sex-linked cognitive tasks, and a sexual attitudes questionnaire. Prenatal androgen levels were indirectly measured by means of the index to ring finger (2D:4D) ratio, and testosterone and progesterone levels were obtained from saliva samples collected at each session from participants who were not using hormonal contraceptives. Results replicate previously reported sex differences in sexual attitudes, sex-linked behaviors and personality traits. More importantly, results provide the first evidence for both pre- and postnatal contributions to sexual attitudes. Men with lower (more male-typical) 2D:4D ratios reported less restricted (more male-typical) sexual attitudes, suggesting that prenatal hormone levels may influence sexual attitudes in adulthood, at least in men. Additionally, the tendency for women who were not using hormonal contraceptives to report less restricted sexual attitudes during the mid-luteal phase of their cycle than during the menstrual phase suggests that changes in circulating sex hormone levels in adulthood, such as those during the menstrual cycle, may influence sexual attitudes in women.

Thesis (M. Med. Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 69-72).

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published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

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Steroid hormones alter the excitability of neural circuits for motor behavior in vertebrates and invertebrates. The insect Manduca sexta, with its well-characterized developmental and endocrinological history, is a useful model system to study these effects. The wandering behavior is a stage-specific locomotor behavior triggered by the steroid hormone 20-hydroxyecdysone (20E) and consists of crawling and burrowing movements as the animal searches for a pupation site.The results of this dissertation show that 20E acts on the isolated larval nervous system to induce wandering activity. The mechanisms underlying the generation of this activity share features similar to other invertebrate systems, including the presence of segmental central pattern generating circuits. The time course for the nervous system response to 20E is long, suggestive of a genomic mechanism of action, and there are no earlier rapid effects of 20E on the intrinsic membrane properties of the abdominal motoneurons. The site of 20E action in inducing wandering locomotion is unlikely to be the abdominal motoneurons, but interneurons presynaptic to these motoneurons. One possible site of 20E action is the brain, which shows stage-dependent expression of ecdysteroid receptors in certain populations of neurons.Descending regulation by the brain and subesophageal ganglion (SEG) is exerted over the segmental motor circuits for crawling and burrowing and reflects stage-dependent differences. Prior to wandering, the brain exerts inhibition over the segmental motor circuits for crawling, but this inhibition is not present during wandering. Removal of the brain, SEG, and thoracic ganglia during on-going fictive locomotion alters the phase relationships between abdominal segments. Further alterations of fictive crawling motor output are observed in more reduced preparations, indicating the importance of intact connections between abdominal ganglia in the production of a reliable motor program. The SEG drives the fictive burrowing motor program. The burrowing motor program is more robustly expressed in nerve cords from wandering larvae, suggesting a stage-dependent difference due to 20E exposure. Subsequent future experiments will use electrophysiological methods and genetic manipulations in Manduca sexta and Drosophila melanogaster, respectively, to explore target sites for hormone action in the brain and the characterization of brain neurons that drive wandering behavior.

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