Infertility in transgenic female mice with human growth hormone expression: evidence for luteal failure.
Introduction of the human growth hormone (hGH) gene fused with mouse metallothionein I promoter into domestic mice leads to ectopic synthesis of hGH, marked stimulation of somatic growth, and female sterility. Transgenic females (produced by mating transgenic males to normal females) mated but failed to become pregnant or pseudopregnant as evidenced by the recurrence of vaginal plugs every 5-7 days. Daily injections of 1 mg progesterone, starting on day 1 postcoitum (p.c.), maintained pregnancy, suggesting that the sterility of these animals is due to inadequate luteal function. In ovariectomized female transgenic mice, median eminence (ME) turnover of dopamine (DA) was increased, and plasma prolactin (PRL) levels were reduced, presumably because of the known lactogenic activity of hGH in rodents. From these observations we suspected that either 1) the corpora lutea of these animals are unresponsive to lactogenic hormones, or 2) hGH by stimulating tuberoinfundibular dopaminergic (TIDA) neurons interferes with the increase in PRL release that normally follows mating and this, in turn, leads to luteal failure. To distinguish between these possibilities, transgenic females were treated with PRL-secreting ectopic pituitary transplants from normal females of the same strain on day 1 p.c. Eight of ten treated females became pregnant and delivered litters. We conclude that infertility of transgenic female mice with hGH expression is due to activation of the TIDA system, suppression of endogenous PRL release, and luteal deficiency.
Bartke
A
A
Department of Physiology, School of Medicine, Southern Illinois University, Carbondale 62901-6512.
Steger
R W
RW
Hodges
S L
SL
Parkening
T A
TA
Collins
T J
TJ
Yun
J S
JS
Wagner
T E
TE
D000818:Animals; D003338:Corpus Luteum / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D007247:Infertility, Female / Q000209:etiology*; D008473:Median Eminence / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010060:Ovulation; D011247:Pregnancy; D011388:Prolactin / Q000097:blood
D011388:Prolactin; D013006:Growth Hormone; D004298:Dopamine