Endogenously elevated androgens alter the developmental programming of the hypothalamic-pituitary axis in male mice.

• Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic-pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic-pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Androgen Antagonists

metabolism

Androgens

metabolism

Animals

Aromatase

genetics

metabolism

Castration

Chorionic Gonadotropin

beta Subunit

Human

genetics

metabolism

Follicle Stimulating Hormone

blood

genetics

Gene Expression

Glutamate Decarboxylase

genetics

metabolism

Glycoprotein Hormones

alpha Subunit

genetics

metabolism

Gonadotropin-Releasing Hormone

genetics

metabolism

Humans

Hypothalamo-Hypophyseal System

growth & development

metabolism

Hypothalamus

physiology

Kisspeptins

Luteinizing Hormone

blood

genetics

Male

Mice

Mice

Transgenic

Pituitary Gland

physiology

Proteins

genetics

metabolism

Puberty

physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)