Chopineau M, Martinat N, Marichatou H, Troispoux C, Auge-Gouillou C, Stewart F, Combarnous Y, Guillou F
Station de Physiologie de la Reproduction, Institut National de la Recherche Agronomique, URA INRA/CNRS 1291, Nouzilly, France.
J Endocrinol. 1997 Nov;155(2):241-5. doi: 10.1677/joe.0.1550241.
Horse LH/chorionic gonadotrophin (eLH/CG) exhibits, in addition to its normal LH activity, a high FSH activity in all other species tested. Donkey LH/CG (dkLH/CG) also exhibits FSH activity in other species, but about ten times less than the horse hormone. In order to understand the molecular basis of these dual gonadotrophic activities of eLH/CG and dkLH/CG better, we expressed, in COS-7 cells, hybrids between horse and donkey subunits, between horse or donkey alpha-subunit and human CG beta (hCG beta), and also between the porcine alpha-subunit and horse or donkey LH/CG beta. The resultant recombinant hybrid hormones were measured using specific FSH and LH in vitro bioassays which give an accurate measure of receptor binding specificity and activation. Results showed that it is the beta-subunit that determines the level of FSH activity, in agreement with the belief that it is the beta-subunit which determines the specificity of action of the gonadotrophins. However, donkey LH/CG beta combined with a porcine alpha-subunit exhibited no FSH activity although it showed full LH activity. Moreover, the hybrid between horse or donkey alpha-subunit and hCG beta also exhibited only LH activity. Thus, the low FSH activity of dkLH/CG requires an equine (donkey or horse) alpha-subunit combined with dkLH/CG beta. These results provide the first evidence that an alpha-subunit can influence the specificity of action of a gonadotrophic hormone.
马促黄体素/绒毛膜促性腺激素（eLH/CG）除了具有正常的促黄体素活性外，在所有其他测试物种中还表现出高促卵泡素活性。驴促黄体素/绒毛膜促性腺激素（dkLH/CG）在其他物种中也表现出促卵泡素活性，但比马激素低约十倍。为了更好地理解eLH/CG和dkLH/CG这些双重促性腺激素活性的分子基础，我们在COS-7细胞中表达了马和驴亚基之间、马或驴α亚基与人类绒毛膜促性腺激素β（hCGβ）之间以及猪α亚基与马或驴促黄体素/绒毛膜促性腺激素β之间的杂种。使用特异性促卵泡素和促黄体素体外生物测定法对所得的重组杂种激素进行了测量，这些测定法能够准确测量受体结合特异性和激活情况。结果表明，决定促卵泡素活性水平的是β亚基，这与认为是β亚基决定促性腺激素作用特异性的观点一致。然而，驴促黄体素/绒毛膜促性腺激素β与猪α亚基结合时虽然表现出完全的促黄体素活性，但没有促卵泡素活性。此外，马或驴α亚基与hCGβ之间的杂种也仅表现出促黄体素活性。因此，dkLH/CG的低促卵泡素活性需要一个马属动物（驴或马）的α亚基与dkLH/CGβ结合。这些结果提供了首个证据，表明α亚基可以影响促性腺激素的作用特异性。
