Targeted ablation of gonadotrophs in transgenic mice affects embryonic development of lactotrophs

Ablation of pituitary gonadotrophs was obtained in transgenic mice expressi ng diphtheria toxin A (DTA) under control of the - 313/ + 48 bovine glycopr otein hormone alpha-subunit (alpha SU) promoter, previously shown to be act ive in mouse gonadotrophs but not in thyrotrophs. Development of hormone-pr oducing cell types was assessed on the day of birth by computer-assisted im age analysis on paraffin-embedded, immunostained pituitary sections. Six ou t of 50 transgenic F-o ('founder') mice (3 males and 3 females) showed a ne arly complete disappearance of gonadotrophs but not of thyrotrophs. The num ber of lactotrophs and the relative area occupied by PRL-immunoreactivity w ere significantly reduced in the gonadotroph-depleted mice. The size of lac totroph clusters was smaller in the absence of gonadotrophs. The number and immunoreactive area of corticotrophs and somatotrophs, on the other hand, were not significantly affected by gonadotroph ablation. Based on the repor ted evidence that fetal ovaries do not produce steroid hormones as a result of lack of expression of at least three of the steroidogenic enzymes, P450 scc, P450c17, and P450arom, the present observations can hardly be explaine d by a decline in estrogen levels due to gonadotroph ablation. Rather, the present data indicate that gonadotrophs directly stimulate the development of lactotrophs during fetal and early postnatal life, consistent with previ ous in vitro observations, and/or that gonadotrophs may share a cell-lineag e relationship with a subpopulation of lactotrophs. (C) 1999 Elsevier Scien ce Ireland Ltd. All rights reserved.