Influence of gonadotropin-releasing hormone pulse amplitude, frequency, and treatment duration on the regulation of luteinizing hormone (LH) subunit messenger ribonucleic acids and LH secretion

Abstract

The effects of GnRH pulse amplitude, frequency, and treatment duration on pituitary α and LH β sub-unit mRNA concentrations were examined in castrate-testosterone replaced male rats. Experimental groups received iv GnRH pulses (5, 25, or 125 ng) at 7.5-, 30-, or 120-min intervals for 8, 24, or 48 h. Saline pulses were given to control rats. Acute LH secretion was measured in blood drawn before and 20 min after the last GnRH pulse.In saline controls, α and LH β mRNAs (150 ± 14, 23 ± 2 pg cDNA bound/100 μg pituitary DNA) fell to 129 ± 14 and 18 ± 2, respectively, after 48 h. In animals receiving GnRH pulses (7.5-min intervals), the 125-ng dose stimulated a slight increase (P < 0.01) in α mRNA levels after 8 and 24 h and both LH subunit mRNAs were increased by the 25- and 125-ng doses after 48h. The 30-min pulse interval injections (25- and 125-ng doses) increased LHβ mRNA levels after 8 h, but α mRNAs were not elevated until after 24 h. Maximum (3-fold) increases in α and LH β mRNAs were seen in rats receiving 25-ng pulses every 30 min for 48 h. Using 120-min pulses, LH subunit mRNAs were not increased by any GnRH dose through 48 h. Acute LH release was not seen in rats receiving 5 ng GnRH pulses at any pulse interval. LH release diminished over time in all other treatment groups, except for rats receiving 25-ng pulses every 30 min, where LH secretion was maintained throughout the 48-h study.These data show that a faster pulse frequency (7.5 or 30 min) is required for the stimulation of LH subunit mRNA levels which is seen after 8-24 h of pulsatile GnRH administration. Higher amplitude GnRH stimulation (i.e. 125 ng/pulse) increases LH subunit mRNAs, but LH release declines suggesting inhibitory effects on translational or posttranslational secretory mechanisms. Further, maximal stimulation of LH gene expression and maintenance of LH release is only seen over a narrow range of GnRH signal patterns (amplitude and frequency). © 1988 by The Endocrine Society.