Modifications of the gonadal function in the adult rat after fetal exposure to spironolactone

• Published in: Biology of reproduction Vol. 32; no. 5; pp. 1051 - 1061
• Main Authors: JAUSSAN, V, LEMARCHAND-BERAUD, T, GOMEZ, F
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-06-1985
• Subjects: Animals; Biological and medical sciences; Cell Nucleus - metabolism; Cytosol - metabolism; Female; Fetus - drug effects; Follicle Stimulating Hormone - metabolism; Fundamental and applied biological sciences. Psychology; Genitalia - anatomy & histology; Genitalia - drug effects; Genitalia - physiology; Gonadal Steroid Hormones - blood; Gonadotropin-Releasing Hormone - pharmacology; Luteinizing Hormone - metabolism; Male; Organ Size - drug effects; Pituitary Gland - metabolism; Pregnancy; Prenatal Exposure Delayed Effects; Prolactin - metabolism; Rats; Rats, Inbred Strains; Receptors, Androgen - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Sexual differentiation and maturation. Puberty. Climacterium; Spironolactone - pharmacology; Thyrotropin-Releasing Hormone - pharmacology; Vertebrates: reproduction; Rat; Rodentia; Antihormone; Aldosterone; Male genital system; In utero; Maternal treatment; Pregnancy; Progeny; Vertebrata; Mammalia; Spironolactone; Gonad; Adult animal; Female genital system; Fetus; Antagonist
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod32.5.1051

The effects of fetal exposure to spironolactone (SPL), an aldosterone antagonist with weak antiandrogen and gestagen properties,
upon the pituitary-gonadal axis were studied in the offspring of rats that had been treated daily from gestation day 14 to
day 20 with 10 or 20 mg SPL or the solvent vehicle (for controls). At 70-80 days of age, SPL-exposed rats showed no alterations
in external genitalia or in body weight. However, males displayed a dose-dependent decrease in the weights of the ventral
prostate and seminal vesicles. Whereas basal and gonadotropin-releasing hormone (GnRH)-induced plasma luteinizing hormone
(LH), follicle-stimulating hormone (FSH), testosterone, and 5 alpha-dihydrotestosterone levels were similar to controls, basal
plasma and pituitary prolactin (Prl) levels were reduced (SPL-exposed 6.8 +/- 1.0 vs. controls 15.8 +/- 2.8 ng/ml and 6.1
+/- 1.2 vs. 11.6 +/- 1.8 microgram/anterior pituitary gland; mean +/- SEM). Cytosolic androgen receptors in ventral prostate
were nonsignificantly decreased, but they increased after GnRH in contrast to controls. Nuclear androgen receptors were normal.
Females displayed normal estrous cycles. Basal and GnRH-induced plasma FSH, Prl, estradiol, and progesterone concentrations
were similar to controls, whereas plasma LH was elevated. Estrogen receptors in uterine cytosol were low and increased after
GnRH. Ovaries and uteri were enlarged. The present study demonstrates that in utero exposure to SPL leads to endocrine dysfunctions
that persist into adulthood. They are characterized in males by hypoprolactinemia, reduced weights of accessory sex organs,
and a suggestion of functional modifications of androgen receptors. In females they are characterized by increased LH secretion,
increased ovarian and uterine weights, and decreased uterine cytosol estrogen receptors, suggesting enhanced estrogenic action.