The aging reproductive neuroendocrine axis.
It is well known that the reproductive system is one of the first biological systems to show age-related decline. While depletion of ovarian follicles clearly relates to the end of reproductive function in females, evidence is accumulating that a hypothalamic defect is critical in the transition from cyclicity to acyclicity. This minireview attempts to present a concise review on aging of the female reproductive neuroendocrine axis and provide thought-provoking analysis and insights into potential future directions for this field. Evidence will be reviewed, which shows that a defect in pulsatile and surge gonadotropin hormone-releasing hormone (GnRH) secretion exists in normal cycling middle-aged female rats, which is thought to explain the significantly attenuated pulsatile and surge luteinizing hormone (LH) secretion at middle-age. Evidence is also presented, which supports the age-related defect in GnRH secretion as being due to a reduced activation of GnRH neurons. Along these lines, stimulation of GnRH secretion by the major excitatory transmitter glutamate is shown to be significantly attenuated in middle-aged proestrous rats. Corresponding age-related defects in other major excitatory regulatory factors, such as catecholamines, neuropeptide Y, and astrocytes, have also been demonstrated. Age-related changes in hypothalamic concentrations of neurotransmitter receptors, steroid receptors, and circulating steroid hormone levels are also reviewed, and discussion is presented on the complex interrelationships of the hypothalamus-pituitary-ovarian (HPO) axis during aging, with attention to how a defect in one level of the axis can induce defects in other levels, and thereby potentiate the dysfunction of the entire HPO axis.
Brann
Darrell W
DW
Institute of Medicine and Genetics, Institute of Neuroscience, Developmental Neurobiology Program, Department of Neurology, Medical College of Georgia, Augusta, GA 30912-3000, USA. dbrann@mail.mcg.edu
Mahesh
Virendra B
VB
D000375:Aging; D000818:Animals; D025461:Feedback, Physiological; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006062:Gonadotropins / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008954:Models, Biological; D009474:Neurons; D009490:Neurosecretory Systems / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010053:Ovary / Q000502:physiology; D051381:Rats; D012098:Reproduction / Q000502:physiology*
D006062:Gonadotropins; D018377:Neurotransmitter Agents; D007987:Gonadotropin-Releasing Hormone