Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Modifications of the gonadal function in the adult rat after fetal exposure to spironolactone. 392 11

Partially-purified 5 alpha-dihydrotestosterone-receptor (DHT-R) complexes, extracted from normal genital skin fibrolasts (GSF) previously labelled with [3H]DHT, dissociate with monophasic kinetics and dissociation rate constants (k-2) of 10, 6, 3 and 2 x 10(-3) min-1 at 40, 37, 32 and 29 degrees C, respectively. An Arrhenius plot yields an activation energy of 28 kcal/mole. We studied 2 subjects who have constitutional androgen insensitivity (AI) despite a normal level of specific DHT-R activity in their GSF. Subject 1 has complete AI and unambiguous female external genitalia; subject 2 has partial AI and had ambiguous external genitalia at birth. In contrast to normal, the DHT-R complexes extracted from the GSF of these 2 subjects dissociate with biphasic kinetics. At 37 degrees C the k-1 of their early ('fast') component is 21 +/- 0.4(+/-SEM) x 10(-3) min-1(n = 7), while that of their late ('slow') component (k-2) is 7.8 +/- 0.3 x 10(-3) min-1 (n = 7). The latter value is very similar to the single k-2 (6.1 +/- 0.1 x 10(-3) min-1, n = 9) of the DHT-R complexes extracted from normal fibroblasts. When dissociation of DHT-R complexes is studied with intact fibroblasts, monophasic kinetics are observed for both the normal and mutant subjects. A k-1 of 18 x 10(-3) min-1 was previously observed for both mutant subjects at 37 degrees C (normal: K-2, 5.9 +/- 0.3 x 10(-3) min-1, n = 15). At 40 degrees C subject 1 has a rate constant of 25 while that of subject 2 is 50 x 10(-3) min-1(normal: 10 x 10(-3) min-1). An Arrhenius plot of the results from subject 1 yields an activation energy of 18 kcal/mole. The 2 sets of data suggest that inability of DHT-R complexes to transform from a rapidly dissociating to a slowly-dissociating form within intact target cells is a marker of genetic mutations that alter the androgen receptor and thereby cause certain types of partial of complete AI.
 ...
PMID:Defective activation of androgen-receptor complexes: a marker of androgen insensitivity. 705 33

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.
 ...
PMID:Studies of the oestrous cycle, oestrus and pregnancy in the koala (Phascolarctos cinereus). 1100 45