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ing to the occurrence of the ovulatory LH surge.
This suppression is postulated to be exerted by
b-endorphin originating in arcuate nucleus neurons
and acting via mu-opioid receptors. However, the
potential involvement of other opioid peptides and
their receptors in “disinhibition” of the LH surge
remained to be explored.
Recent work in my laboratory suggested that a
reduction in medial preoptic area (MPOA) kappaopioid
receptor-mediated inhibitory tone may also
be a critical event in generation of the LH surge, as
pharmacological blockade of kappa-opioid receptors
with norbinaltorphimine at this CNS site late on
the morning of proestrus prematurely advanced the
ovulatory LH surge. Dynorphin is the endogenous
ligand for the kappa-opioid receptor, and very little
is known about the role of the prodynorphin family
of endogenous opioid peptides in reproductive neuroendocrine
function. Additional studies demonstrated
that prodynorphin-derived peptides, acting
through kappa-opioid receptors, block the LH surge
and ovulation. Dynorphin A1-17 and A1-8 are the
most potent in this regard. Neutralization of these
peptides, by push-pull perfusion of the MPOA on
the morning of proestrus with antibodies (Ab) specific
for each peptide, resulted in some animals in
an advancement in the time of LH release sufficient
to cause ovulation. This suggested that these two
peptides might have a role in the MPOA, although
a minor one, in suppressing LH secretion early
on proestrus. A reduction in prodynorphin gene
expression on the afternoon of proestrus may be
one event involved in a possible decrease in dynorphin
inhibitory tone on the ovulatory LH surge-generating
signal. However, a complete loss of kappaopioid
inhibition is not required for the onset of the
LH surge. These experiments have broadened our
understanding of the role of the prodynorphin family
of opioid peptides in reproductive neuroendocrine
function by clarifying their role in the mechanisms
regulating the ovulatory LH surge.
Selected Publications
Smith, M.J., and R.V. Gallo. (1997). The effect of blockade
of kappa-opioid receptors in the medial preoptic area on the
luteinizing hormone surge in the proestrous rat. Brain Research
768: 111-119.
Zhang, Q., and R.V. Gallo. (2002). Effect of prodynorphinderived
opioid peptides on the ovulatory luteinizing hormone
surge in the proestrous rat. Endocrine 18: 27-32.
Zhang, Q., J. M. McCoy, and R. V. Gallo. (2002). Further studies
on possible dynorphin involvement in the ovulatory luteinizing
hormone surge in the proestrous rat. Endocrine 18: 231-238.
Zhang, Q., and R. V. Gallo. (2003). Presence of kappa-opioid
inhibitory tone at the onset of the ovulatory luteinizing hormone
surge in the proestrous rat. Brain Research 980: 135-139.