Targeted overexpression of calcitonin in gonadotrophs of transgenic mice leads to chronic hypoprolactinemia.
It was previously shown that calcitonin-like pituitary peptide (pit-CT) is synthesized and secreted by gonadotrophs, and pit-CT inhibits PRL gene transcription and lactotroph cell proliferation. Present studies examined long-term consequences of pit-CT overexpression on the functioning of mouse anterior pituitary (AP) gland. Targeted overexpression of pit-CT in gonadotrophs of mouse pituitaries was achieved by generating mice overexpressing bovine luteinizing hormone (LH)-alpha subunit promoter-pit-CT cDNA transgene. Transgenic (pit-CT+) mice displayed chronic but selective overexpression of pit-CT in gonadotrophs. The mice also displayed a dramatic decline in PRL gene expression as assessed by PRL mRNA abundance, PRL immunohistochemistry (IHC) and serum PRL levels. LH secretion in pit-CT+ mice was also reduced, without any change in FSH secretion. Reproductive abnormalities such as prolonged estrous cycles, reduced pregnancy rate, delivery of smaller litters, increased neonatal mortality and deficient lactation were also observed. Administration of PRL during early pregnancy significantly increased the pregnancy rate and neonatal survival of newborns. These results demonstrate that overexpression of pit-CT leads to chronic hypoprolactinemia and reproductive dysfunction in female mice, and reinforces the possibility that gonadotroph-derived pit-CT is an important paracrine regulator of lactotroph function.
Yuan
Ren
R
Department of Pharmaceutical Sciences, University of Louisiana School of Pharmacy, 700 University Avenue, Monroe, LA 71209, USA.
Kulkarni
Trupti
T
Wei
Fu
F
Shah
Girish V
GV
D000818:Animals; D002116:Calcitonin / Q000235:genetics / Q000502:physiology*; D002417:Cattle; D002908:Chronic Disease; D018076:DNA, Complementary / Q000235:genetics; D030762:Estrous Cycle; D005260:Female; D018390:Gene Targeting; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics* / Q000378:metabolism*; D007247:Infertility, Female / Q000209:etiology; D007774:Lactation / Q000235:genetics; D008098:Litter Size; D051379:Mice; D008822:Mice, Transgenic; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D018873:Pregnancy Rate; D011388:Prolactin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D019076:Transgenes / Q000502:physiology
D018076:DNA, Complementary; D015292:Glycoprotein Hormones, alpha Subunit; D011388:Prolactin; D002116:Calcitonin