Ebb Tide: Brain center linked to decrease in egg-producing waves

R. John Davenport

Key Words: luteinizing hormone • LH surge • menopause • endocrine • Fos • AVPv

Abstract: As mammals age, one of the first things to go is reproductive capacity. Ovulation becomes irregular, because waves of luteinizing hormone (LH) don't crest as high as before. New results indicate that a reduction in nerve impulses from a particular part of the brain is partly responsible for lowering the levels of the hormone that triggers LH production.

Release of luteinizing hormone-releasing hormone (LH-RH) from neurons in the hypothalamus, a part of the brain that governs a host of hormone-controlled bodily functions, spurs the pituitary gland to produce waves of LH. These so-called LH surges stimulate egg release from the ovaries, but they diminish during aging because production of LH-RH by hypothalamic neurons decreases. Exactly what causes this decline is unknown, but some suspect that neurons from elsewhere in the hypothalamus might be to blame. Previous work implicated a region known as the AVPv: AVPv nerve cells connect to LH-RH-producing neurons, and damaging the AVPv blocks LH surges. But it hasn't been clear if a decrease in AVPv activity with advancing years prevents LH-RH synthesis.

In search of a missing link, Le and colleagues looked for activity in AVPv and LH-RH neurons in the brains of young and middle-aged rats sacrificed in the midst of an LH surge. The team used antibodies to detect the presence of the Fos protein, an indicator of neuron activity. A smaller percentage of LH-RH neurons in middle-aged rat brains contained Fos as compared with young rat brains. In addition, a similarly reduced fraction of neurons in the AVPv region of middle-aged brains lit up with Fos. The researchers then damaged AVPv in young rats and monitored LH-RH neuron activity. LH-RH neurons on the same side of the brain as the lesion took a hit, expressing no Fos; LH-RH neurons on the uninjured side of the brain carried on normally. The results add to evidence that nerves in the AVPv stimulate LH-RH production. They also suggest that reduced AVPv firing accounts in part for the waning LH-RH production--and, in turn, the declining LH and loss of ovulation--that comes with age.

Why AVPv activity falls over time is unclear, and the answer is not likely to be simple. The AVPv takes in signals from multiple hormones and neurons, so the change probably involves more than one trigger. And other brain centers could play roles as well. Further elucidating this pathway will help researchers understand how once-swelling hormonal seas flatten.

--R. John Davenport

W.-W. Le, P. M. Wise, A. Z. Murphy, L. M. Coolen, G. E. Hoffman, Parallel declines in Fos activation of the medial anteroventral periventricular nucleus and LHRH neurons in middle-aged rats. Endocrinology 142, 4976-4982 (2001). [Abstract] [Full Text]

Citation: R. J. Davenport, Ebb Tide: Brain center linked to decrease in egg-producing waves. Science's SAGE KE (7 November 2001), http://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/6/nw21