Abstract:
:Female infertility is often associated with deregulation of hormonal networks, and hyperprolactinemia is one of the most common endocrine disorders of the hypothalamic-pituitary axis affecting the reproductive functions. We have shown previously that transgenic female mice overexpressing human chorionic gonadotropin β-subunit (hCGβ+ mice), and producing elevated levels of bioactive LH/hCG, exhibit increased production of testosterone and progesterone, are overweight and infertile, and develop hyperprolactinemia associated with pituitary lactotrope adenomas in adult age. In the present study, we analyzed the influence of the hyperprolactinemia of hCGβ+ females on their reproductive phenotype by treating them with the dopamine agonists, bromocriptine and cabergoline. Long-term bromocriptine treatment of adult mice was effective in the control of obesity, pituitary growth, and disturbances in the hormone profile, demonstrating that hyperprolactinemia was the main cause of the hCGβ+ female phenotype. Interestingly, short-term treatment (1 wk) with cabergoline applied on 5-wk-old mice corrected hyperprolactinemia, hyperandrogenism, and hyperprogesteronemia, prevented pituitary overgrowth, normalized gonadal function, and recovered fertility of adult hCGβ+ females after hormone-induced and natural ovulation. The same cabergoline treatment in the short term applied on 3-month-old hCGβ+ females failed to recover their reproductive function. Hence, we demonstrated that the short-term cabergoline treatment applied at a critical early stage of the phenotype progression effectively prevented the hyperprolactinemia-associated reproductive dysfunction of hCG-overproducing females.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Ratner LD,Gonzalez B,Ahtiainen P,Di Giorgio NP,Poutanen M,Calandra RS,Huhtaniemi IT,Rulli SBdoi
10.1210/en.2012-1393subject
Has Abstractpub_date
2012-12-01 00:00:00pages
5980-92issue
12eissn
0013-7227issn
1945-7170pii
en.2012-1393journal_volume
153pub_type
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