Chronological changes in sex steroid, gonadotropin and prolactin secretions in aging female rats displaying different reproductive states.
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Biomedical subjects
Publications and source records attributed to B R Hopper.
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The incidence of senescent anovulation (constant estrus) in female rats increases sharply in the age interval 10--14 months. We have compared the neuroendocrine status of 12-month-old rats, which were still cycling, with that of 6-month-old rats in the reproductive prime. Norepinephrine content in the median eminence of the hypothalamus and circulating levels of FSh and androstenedione were significnatly higher in middle-aged rats (12 months old) than in young controls (6 months old). These increases were selective, in that ten other neuroendocrine parameters measured were unchanged. These results indicate that changes occur at multiple levels of the neuroendocrine system during the transitional phase prior to the onset of senescent anovulation.
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A simple method is described for the simultaneous radioligand assay of four delta5-3beta-hydroxysteroids adjacent to one another on the biosynthetic pathway (pregnenolone [1], 17alpha-hydroxypregnenolone, dehydroepiandrosterone and 5-androsterone-3beta, 17beta-diol), and their four delta4-3keto products (progesterone, 17alpha-hydroxyprogesterone, 4-androstene-3, 17-dione and testosterone). Two plasma aliquots are extracted and fractionated each for four steroids and individual corrections are made for losses. For fractionation, maximum use is made of the high resolution and reproducibility of celite minicolumns, using propylene glycol as stationary phase, and a discontinuous gradient of ethyl acetate in iso-octane as mobile phase. The fractions are then assayed in the appropriate radioligand end-assay system. Each assay was finally validated by demonstrating coincidence of peaks of immuno- and radioactive steroid in extracts of female plasma. Results in pre-pubertal girls and women in the follicular phase of the menstrual cycle suggest that the major change in adrenal steroid production at puberty may be an increase in 17, 20-desmolase activity. There appears to be little reversal of this change in adrenal function after ovariectomy.
In order to quantitate the chronological change in circulating dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DS) levels during the period of sexual maturation, serum DHEA and DS concentration (3-5 PM) in 76 boys and 65 girls (ages 8 to 15) as well as in adult male and female subjects were measured by a specific and sensitive radioimmunoassay technique. Our data show a progressive and parallel increase in serum DHEA and DS concentrations in boys, and adult male levels were reached earlier for DHEA (age 13) than for DS (age 14). From age 8 to adult male, there was a 2.6-fold increase in DHEA (1.52 plus or minus 0.16 ng/ml to 3.91 lus or minus 0.34 ng/ml) and a 7.7-fold increase in DS (0.40 plus or minus 0.08 mug/ml to 3.09 plus or minus 0.36 mug/ml). The rise of DHEA and DS was not in a parallel fashion in girls; while DS rose progressively, DHEA showed an abrupt increase between 11 and 12 yr of age. Adult female range was reached by age 12 for DHEA and by age 15 for DS. From age 8 to adultfemale there was a 2.3-fold increase in DHEA (1.93 plus or minus 0.19 ng/ml to 4.49 plus or minus 0.76 ng/ml) and a 7.5-fold increase in DS (0.29 PLUS OR MINUS 0.05 MUg/ml to 2.17 plus or minus 0.34 mug/ml). The role of increased adrenal androgens inthe sexual development during early stages of puberty is discussed.
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