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Naloxone Increases the Frequency of Pulsatile Luteinizing Hormone Secretion in Women with Hyperprolactinemia^*

CURTISS B. COOK, TODD B. NIPPOLDT, GAD B. KLETTER, ROBERT P. KELCH and JOHN C. MARSHALL

Divisions of Endocrinology, Departments of Internal Medicine and Pediatrics, University of Michigan Ann Arbor, Michigan 48109

Address requests for reprints to Dr. Robert P. Kelch, Department of Pediatrics, C. S. Mott Childrens Hospital, Box 0718, D3202, Ann Arbor, Michigan 48109-0718.

The ability to change the frequency and amplitude of pulsatile GnRH secretion may be an important mechanism in maintaining regular ovulatory cycles. Hyperprolactinemia is associated with anovulation and slow frequency LH (GnRH) secretion in women. To assess whether the slow frequency of LH (GnRH) secretion is due to increased opioid activity, we examined the effect of naloxone infusions in eight amenorrheic hyperprolactinemic women (mean ± SE, serum PRL, 160 ± 59 µg/L).

After a baseline period, either saline or naloxone was infused for 8 h on separate days, and LH was measured in blood obtained at 15-min intervals. Additional samples were obtained for plasma FSH, PRL, estradiol, and progesterone. Responses to exogenous GnRH were assessed at the end of the infusions.

LH pulse frequency increased in all subjects from a mean of 4.0 ± 0.5 pulses/10 h (mean ± SE) during saline infusion to 8.0 ± 1.0 pulses/10 h during naloxone infusion (P < 0.01). LH pulse amplitude did not change, and mean plasma LH increased from 7.4 ± 0.8 IU/L (±SE) to 11.2 ± 1.5 IU/L during naloxone (P < 0.01). A small but significant increase was seen in mean plasma FSH. Plasma PRL, estradiol, and progesterone were unchanged by naloxone infusion.

These data suggest that elevated serum PRL reduces the frequency of LH (GnRH) secretion by increasing hypothalamic opioid activity and suggest that the anovulation in hyperprolactinemia is consequent upon persistent slow frequency LH (GnRH) secretion.

^* This work was supported by USPHS Grants HD-16000 and CRC Grant 5M01-RR-42.

Supported by Institutional Training Grant 5-T32-AG-00123-05.

Supported by an individual National Research Scientist Award lf-32-HD-07029-01.

Received January 11, 1991.

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