Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance ....Reproduction is dependent upon the secretion of gonadotropin releasing hormone (GnRH) from the brain, that stimulates gonadotropin synthesis and release from the pituitary gland. In turn, GnRH and gonadotropin secretion is controlled by feedback effects of gonadal steroids such as estrogen. Various neural systems regulate GnRH cells. Kisspeptin is a recently discovered neuropeptide that appears to play a major role in the regulation of GnRH cells. Because it is newly recognized, the significance of kisspeptin and the relevant receptor, GPR54, is not well defined. This project aims to use our unique combination of abilities to determine the significance of kisspeptin in the regulation of GnRH and gonadotropin secretion. We will study both sheep and monkey brains, measuring gene expression for kisspeptin and GPR54 in a range of physiological states and we will determine how kisspeptin acts on GnRH cells. We will determine whether kisspeptin plays a role in the feedback effects to GnRH cells. Effects on the pituitary gland will also be studied. We will use sheep models to measure kisspeptin effects on GnRH secretion, because this cannot be done in the monkey or the rodent. We will examine the function of kisspeptin and GPR54 in relation to puberty. We will also use a model of puberty (seasonal breeding in the sheep) to determine whether activation and quiescence of the reproductive system is related to the function of kisspeptin and GPR54. This work will define the role of kisspeptin in the regulation of reproduction.Read moreRead less
Effect Of Testosterone Treatment Combined With Dietary Restriction On Body Fat Mass And Muscle Function In Obese Men: A Randomized Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Obesity, an increasing health and economic burden, is associated with lowered testosterone levels in men. While both dietary restriction and testosterone treatment reduce body fat, whether a combination of these two approaches achieves a more pronounced fat mass reduction is unknown. We will conduct a rigorous 12 month clinical trial of testosterone treatment in 150 obese men with a low testosterone level. All men will receive dietary intervention to induce and maintain weight loss
The Effect Of Testosterone Treatment In Men With Type 2 Diabetes And Low Normal Total Testosterone Levels
Funder
National Health and Medical Research Council
Funding Amount
$65,658.00
Summary
This trial will assess the effect of testosterone injections in men with type 2 diabetes and low testosterone levels on control of their diabetes, resistance to insulin and the metabolic syndrome (obesity, high blood pressure, high cholesterol). Results from this trial will clarify if there is a role for testosterone treatment in men with type 2 diabetes.
Neuroendocrine Functions Of PrRP, A Novel Hypothalamic Peptide
Funder
National Health and Medical Research Council
Funding Amount
$183,928.00
Summary
This project investigates the role of a newly discovered chemical (peptide) that is found in a part of the brain called the hypothalamus which regulates the activity of the pituitary gland. The hypothalamus and pituitary gland work together to control many of the body?s essential processes such as growth, metabolism and reproduction. Some human diseases are caused by abnormalities of the hypothalamus and pituitary gland while many other diseases affect the functions of these glands, leading to w ....This project investigates the role of a newly discovered chemical (peptide) that is found in a part of the brain called the hypothalamus which regulates the activity of the pituitary gland. The hypothalamus and pituitary gland work together to control many of the body?s essential processes such as growth, metabolism and reproduction. Some human diseases are caused by abnormalities of the hypothalamus and pituitary gland while many other diseases affect the functions of these glands, leading to widespread complications such as weight loss, wasting, abnormal immune responses, infertility or failure of lactation. While many of the hormones and chemicals of the hypothalamus and pituitary gland have been extensively studied, recent advances in molecular biology have led to the discovery of new chemicals that may have important regulatory functions. One of these newly discovered substances which was named Prolactin-Releasing Peptide or PrRP is the topic of this project. PrRP will be tested in a series of experiments in animals in order to determine how important it is in regulating the pituitary gland, particularly in stress and during lactation which are conditions when PrRP could be secreted. It is hoped that this research will lead to a more detailed understanding of how the reproductive and endocrine system are controlled in humans and to new methods for the manipulation of these systems under normal and disease conditions.Read moreRead less
Do PACAP-containing Neurons In The Hypothalamus Regulate Reproductive Hormone Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$182,559.00
Summary
This project investigates the role of a brain chemical called PACAP which is found in a part of the brain called the hypothalamus which regulates the reproductive system. The hypothalamus does this by controlling the secretion of several pituitary gland hormones, LH and prolactin, which in turn stimulate normal function of the ovaries or testes. Abnormal secretion of these hormones is seen in conditions such as anorexia nervosa, bulimia, stress, critical illness, aging and many others with the r ....This project investigates the role of a brain chemical called PACAP which is found in a part of the brain called the hypothalamus which regulates the reproductive system. The hypothalamus does this by controlling the secretion of several pituitary gland hormones, LH and prolactin, which in turn stimulate normal function of the ovaries or testes. Abnormal secretion of these hormones is seen in conditions such as anorexia nervosa, bulimia, stress, critical illness, aging and many others with the result that patients have low levels of steroids in their blood and inactive gonads, changes which in themselves lead to other health problems. Because these hormones are essential for normal reproduction, it is possible that PACAP may play an important role in regulating this process, both under normal conditions and in disease. It is hoped that this research will lead to a more detailed understanding of how the endocrine system is controlled in humans and to new methods for the manipulation of the reproductive axis, under normal and disease conditions.Read moreRead less
Role Of Non-classical Actions Of Androgens In Musculoskeletal Physiology
Funder
National Health and Medical Research Council
Funding Amount
$703,664.00
Summary
Androgens (male sex hormones) are important for growth-maintenance of muscle and bone. The classical action of androgens is to bind the androgen receptor (AR) and regulate target genes. They can also act via non-classical AR mechanisms through other cellular pathways. To understand the role of non-classical actions in the musculoskeletal system we will study mice in which androgens can only act via this pathway. This knowledge is important for the treatment of osteoporosis and muscle wasting.
Genomic And Non-genomic Actions Of Androgens In Regulation Of Fat Mass And Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$395,421.00
Summary
Men have lower amounts of body fat than women, but are more likely to deposit fat around the stomach and abdominal region than women. This increased abdominal fat in men significantly increases the risk of developing type 2 diabetes and heart disease. The differences between men and women suggest that there is hormonal control of fat development; however, little is known regarding how male sex hormones, androgens, control these processes. We will investigate how androgens control fat formation, ....Men have lower amounts of body fat than women, but are more likely to deposit fat around the stomach and abdominal region than women. This increased abdominal fat in men significantly increases the risk of developing type 2 diabetes and heart disease. The differences between men and women suggest that there is hormonal control of fat development; however, little is known regarding how male sex hormones, androgens, control these processes. We will investigate how androgens control fat formation, and the response of fat and muscle tissue to glucose and insulin, using mutant mouse strains. These mouse strains have a mutation in the androgen receptor, a protein which acts as a key-lock mechanism to allow tissues to respond to androgens. This mutation stops the androgen receptor from functioning, so these mice can be used to determine the function of androgens acting through the androgen receptor. We will study three strains of mutant mice: (i) in which the androgen receptor is non-functional in all tissues of the body; (ii) in which the androgen receptor is non-functional only in fat tissue, but normal in all other tissues; and (iii) in which the androgen receptor is non-functional only in skeletal muscle, but is normal in all other tissues. The aim of our research is to determine the effect of the mutations in these three different mouse lines on paramateres including the amount of fat formed, the site of fat deposition, the levels of lipids and insulin in the blood and their response to glucose. The androgen receptor is a master switch that turns on or off other genes. Therefore, we also aim to identify which genes are controlled by the androgen receptor in fat and muscle. This research will identify how androgens control fat development and function, and will identify genes that mediate these actions in fat and muscle. This will provide potential molecules that could be used therapeutically to treat obesity and prevent type 2 diabetes and heart disease.Read moreRead less
The Molecular Mechanisms Of Anabolic Androgen Actions In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in musc ....We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in muscle. We will study the growth of mouse muscle cells in culture, and measure their rate of growth when treated with androgens. All cells contain certain factors that control their growth and replication, and we will test whether androgens activate these factors to increase growth. We will also study the effect of androgens on muscle in mice, to investigate complex effects that only occur in real muscle. We will neuter male mice, which causes muscle wasting. Neutered mice will then be treated with androgens or placebo, and we will compare the muscle growth effect of androgen treatment versus placebo. We will measure muscle strength, size, and the number of muscle cells in treated and placebo mice. We will also see if the effects of androgen require a particular protein, the androgen receptor, which acts as a lock-key mechanism in cells, to allow them to respond to androgens. We will make a strain of mouse with a non-functional version of the androgen receptor only in muscle cells. This will determine if the muscle growth effects of androgens occur through a direct action on muscle, or indirectly through acting on other tissues in the body. This information will ultimately allow us to design more targeted androgen therapies for muscle wasting, that act only on muscle.Read moreRead less