Androgen Suppresses In Vivo and In Vitro LH Pulse Secretion and Neural Kiss1 and Tac2 Gene Expression in Female Mice

Androgens can affect the reproductive axis of both sexes. In healthy women, as in men, elevated exogenous androgens decrease gonad function and lower gonadotropin levels; such circumstances occur with anabolic steroid abuse or in transgender men (genetic XX individuals) taking androgen supplements....

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2020-12, Vol.161 (12)
Main Authors: Esparza, Lourdes A, Terasaka, Tomohiro, Lawson, Mark A, Kauffman, Alexander S
Format: Article
Language:English
Subjects:
Androgens - pharmacology
Animals
Dihydrotestosterone - pharmacology
Female
Gonadotropin-Releasing Hormone - metabolism
Hypothalamus - drug effects
Hypothalamus - metabolism
Kisspeptins - genetics
Kisspeptins - metabolism
Luteinizing Hormone - blood
Male
Mice
Neurons - drug effects
Neurons - metabolism
Pituitary Gland - drug effects
Pituitary Gland - metabolism
Protein Precursors - genetics
Protein Precursors - metabolism
Signal Transduction - drug effects
Tachykinins - genetics
Tachykinins - metabolism
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Summary:Androgens can affect the reproductive axis of both sexes. In healthy women, as in men, elevated exogenous androgens decrease gonad function and lower gonadotropin levels; such circumstances occur with anabolic steroid abuse or in transgender men (genetic XX individuals) taking androgen supplements. The neuroendocrine mechanisms by which endogenous or exogenous androgens regulate gonadotropin release, including aspects of pulsatile luteinizing hormone (LH) secretion, remain unknown. Because animal models are valuable for interrogating neural and pituitary mechanisms, we studied effects of androgens in the normal male physiological range on in vivo LH secretion parameters in female mice and in vitro LH secretion patterns from isolated female pituitaries. We also assessed androgen effects on hypothalamic and gonadotrope gene expression in female mice, which may contribute to altered LH secretion profiles. We used a nonaromatizable androgen, dihydrotestosterone (DHT), to isolate effects occurring specifically via androgen receptor (AR) signaling. Compared with control females, DHT-treated females exhibited markedly reduced in vivo LH pulsatility, with decreases in pulse frequency, amplitude, peak, and basal LH levels. Correlating with reduced LH pulsatility, DHT-treated females also exhibited suppressed arcuate nucleus Kiss1 and Tac2 expression. Separate from these neural effects, we determined in vitro that the female pituitary is directly inhibited by AR signaling, resulting in lower basal LH levels and reduced LH secretory responses to gonadotropin-releasing hormone pulses, along with lower gonadotropin gene expression. Thus, in normal adult females, male levels of androgen acting via AR can strongly inhibit the reproductive axis at both the neural and pituitary levels.
ISSN:0013-7227
1945-7170
DOI:10.1210/endocr/bqaa191