Effects of luteinizing hormone releasing hormone on the gonadotrophs of hypogonadal (hpg) mice

Hypogonadal (hpg) mice lack hypothalamic luteinizing hormone releasing hormone (LH\x=req-\ RH); consequently the pituitary gonadotrophs, though differentiated, remain inactive. The acute and chronic responses of gonadotrophs in hpg mice to LH-RH were studied using quantitative electron microscopy, immunocytochemistry for LH and radioimmunoassay of the gonadotrophins. Acute i.v. administration of 40 ng LH-RH to male hpg mice produced an eightfold increase in plasma LH after 5 min, but granule depletion was not detectable ultra-structurally. Vacuoles (300\p=n-\600 nm) were present more frequently in gonadotrophs from hpg mice given LH-RH compared with control mice. Daily s.c. administration of 2\g=m\gLH\x=req-\ RH to male hpg mice for 20 days stimulated a 63-fold increase in the pituitary content of FSH but only a twofold increase in the pituitary content of LH. Testicular weight increased fivefold but the weight of the seminal vesicles did not change. The frequency of cells immunoreactive for LH increased ( \m=x\1 \m=.\6),the gonadotrophs hypertrophied ( \m=x\1 \m=.\9)and the cell content of granules increased ( \m=x\2\m=.\3)to values close to the normal range. The rough endoplasmic reticulum and Golgi apparatus became more prominent. A striking result of long-term daily administration of LH-RH was the accumulation of large (1\p=n-\2\g=m\m)lipid droplets in about 40 % of gonadotrophs. All these changes induced by LH-RH regressed towards the untreated hpg state when LH-RH administration was discontinued for 5 and 10 days. These results show that the gonadotrophs of hpg mice can be stimulated trophically by LH-RH, and that long-term administration stimulates the synthesis and release of the gonadotrophins but the effect on FSH is much greater than on LH