Induced ablation of gonadotropins in transgenic mice expressing herpes simplex virus thymidine kinase under the FSH beta-subunit promoter.
Suppression of gonadotropins was induced by gancyclovir or acyclovir treatment in transgenic mice carrying 2.3 kb of bovine follicle-stimulating hormone beta (FSH beta) promoter fused to Herpes simplex virus thymidine kinase (tk) coding sequence. Transgenic tk and endogenous FSH beta were immunohistochemically co-localized in the same pituitary cells. In adult castrated transgenic males, gancyclovir treatment reduced plasma FSH (30%, P < 0.001). In intact juvenile gancyclovir treated mice, the reduction of pituitary FSH, and in males also of plasma FSH, was greater (50-70%, P < 0.05-0.01). A concomitant suppression of luteinizing hormone (LH) (50%, P < 0.01) was observed in female pups. The most pronounced reduction of gonadotropins was observed in newborn transgenic pups treated in utero with acyclovir. Both males and females had significantly lower pituitary levels of FSH (75-55%), LH (80-90%) or both (P < 0.05-0.01). Less pronounced decreases (30-40%, P < 0.01) were observed in plasma FSH. No apparent defects were seen in the testes of the transgenic, acyclovir treated, newborn pups. This mouse model is applied to study the dynamics of the gonadotropes and the role of gonadotropins in the maturation of the reproductive functions.
Markkula
M
M
Department of Physiology, University of Turku, Finland.
Kananen
K
K
Paukku
T
T
Männistö
A
A
Loune
E
E
Fröjdman
K
K
Pelliniemi
L J
LJ
Huhtaniemi
I
I
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis / Q000097:blood / Q000235:genetics*; D015774:Ganciclovir / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006062:Gonadotropins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013006:Growth Hormone / Q000032:analysis; D007986:Luteinizing Hormone / Q000032:analysis / Q000097:blood; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011388:Prolactin / Q000032:analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology*; D013737:Testis / Q000201:enzymology; D013937:Thymidine Kinase / Q000032:analysis / Q000235:genetics*; D013972:Thyrotropin / Q000032:analysis
D017931:DNA Primers; D006062:Gonadotropins; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D004247:DNA; D013937:Thymidine Kinase; D015774:Ganciclovir; D000212:Acyclovir