Lamprey Gonadotropin Hormone-Releasing Hormone-III has No Selective Follicle-Stimulating Hormone-Releasing Effect In Rats

Lamprey gonadotropin releasing‐hormone (LGnRH)‐III, a hypothalamic neurohormone recently isolated from sea lamprey, was reported to have a selective stimulatory effect on follicle‐stimulating hormone (FSH) release in rats and suggested to be the mammalian FSH‐releasing factor. In this study, we determined the relative luteinizing hormone (LH)‐ and FSH‐releasing potency of LGnRH‐III compared to mammalian gonadotropin‐releasing hormone (LHRH) in normal female rats, ovariectomized (OVX) and oestrogen/progesterone substituted rats and the superfused rat‐pituitary cell system. The specificity of LGnRH‐III for the mammalian LHRH receptor was investigated by blocking the receptor with an LHRH antagonist, MI‐1544. In vitro, LGnRH‐III dose‐dependently stimulated both LH and FSH secretion from rat pituitary cells at 10−7 to 10−5 M concentrations, while LHRH stimulated gonadotropin secretion at a 1000‐fold lower doses (10−10 to 10−8 M). The difference between its LH‐ and FSH‐releasing potency was similar to that of LHRH. LGnRH‐III bound to high affinity binding sites on rat pituitary cells with a Kd of 6.7 nm, Bmax=113±27 fmol/mg protein. In vivo, LGnRH‐III also stimulated both LH and FSH secretion in a dose‐dependent manner and, similar to LHRH, induced a greater rise in the serum LH than the FSH level. In normal cycling rats, it showed 180–650‐fold weaker potency than LHRH in stimulating LH secretion and 70–80‐fold weaker effect in stimulating FSH secretion. In OVX rats, LGnRH‐III demonstrated a similarly weak effect on both gonadotropins. It was found to be 40–210‐fold less potent than LHRH regarding LH release and 50–160‐fold weaker regarding FSH release. LHRH‐receptor antagonist MI‐1544 prevented both the LH‐ and the FSH‐releasing effect of LGnRH‐III both in vitro and in vivo. These results do not support the hypothesis that LGnRH‐III might be the mammalian FSH‐releasing factor but demonstrate that it is a weak agonist for the pituitary LHRH receptor and stimulates both gonadotropins in a dose‐dependent fashion.