The interaction of testosterone with the brain of the orchidectomized primate fetus

Michael, Richard P.; Zumpe, Doris; Bonsall, Robert W.

doi:10.1016/0006-8993(92)90565-q

Cited by 6 publications

(5 citation statements)

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“…To investigate developmental changes in the week immediately after birth, we adminis tered [3H]-Tto male and female cynomolgus monkey neo nates 3 days after gonadectomy and examined the uptake of radioactivity by subcellular fractions of brain, pituitary gland and genital tract using high performance liquid chromatography (HPLC). The present findings are com pared with those from fetuses at 122 days gestation [14] and with those from fully adult males [16].…”

supporting

confidence: 65%

“…A comparison has been made in male cynomolgus monkeys of results (1) from orchidectomized fetuses (n = 5) at around 122 days gestation [14], (2) from the or- chidectomized neonates (n = 4) reported here, and (3) from fully adult castrates (n = 4) [16]. Fetuses received subcutaneous injections of 500 pCi [3H]-T (2.3 pCi/g body weight), neonates received subcutaneous injections of 500 pCi [3H]-T (1.2 pCi/g), and adults received in travenous injections of 3 mCi [3H]-T (0.6 pCi/g).…”

Section: Comparisons Between Fetuses Neonates and Adultsmentioning

confidence: 99%

“…Administration of [3H]-testosterone (['H]-T) to the adult macaque has revealed a system of neurons, mostly within the hypothalamus, preoptic area and amygdala, that concentrates T or its metabolites [9][10][11], Chromatographic analysis of purified nuclear pellets taken from these regions showed that more than 50% of the radioactivity was in the form of [3H]-estradiol ([3H]-E2) produced by aromatization of [3H]-T: the principal radioactive androgen present was [3H]-T itself rather than [3H]-dihydrotestosterone ([3H]-DHT) as in the genital tract. The uptake of [3H]-Thas recently been studied in the fetal macaque at about 120 days gestation [12][13][14] when plasma T levels in males are usually high [15], and most of the regions that concentrated [3H]-T or its metab olites in the adult also did so in the fetus, although per centages of cells labeled in autoradiograms were generally much lower in the fetus. In nuclear pellets from the fetal hypothalamus, most of the radioactivity was in the form of [3H]-E2 as in the adult.…”

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Developmental Changes in the Uptake of Testosterone by the Primate Brain

Bonsall

Michael²

1992

Neuroendocrinology

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During the neonatal period in male macaques, the testis produces adult-like levels of plasma testosterone (T), but the function of this in development is not understood. To investigate the interaction of T with the neonatal brain, 4 male and 5 female cynomolgus monkeys were gonadectomized 2-5 days after birth, and were injected subcutaneously 3 days later with 500 µCi [³H]-testosterone ([³H]-T). 60 min later, brains and other tissue samples were removed. Purified nuclear pellets were prepared by centrifugation through 2 M sucrose, extracted into ether and analyzed by high-performance liquid chromatography. The aromatized metabolite, [³H]-estradiol ([³H]-E2), was found only in the hypothalamus (HYP) and amygdala (AMG). In HYP, [³H]-E2 represented 55 ± 3% of the radioactivity in males and 53 ± 3% in females. In AMG, [³H]-E2 represented 40 ± 9% of the radioactivity in males and 47 ± 3% in females. Concentrations of unchanged [³H]-T were higher than those of [³H]-dihydrotestosterone ([³H]-DHT). Both androgens were present in nuclear pellets from all 8 brain regions studied, and concentrations were significantly higher in females than in males (p < 0.005). [³H]-T was also the main form of radioactivity in nuclear pellets from pituitary gland, adrenal gland, uterus and liver, but very high levels of [³H]-DHT were found in seminal vesicles, prostate and penis. Comparisons were made with previous results from orchidectomized fetuses at 122 days gestation and from fully adult male castrates, and the largest developmental changes occured in the AMG where concentrations of [³H]-E2 were 20-fold higher in adults than in fetuses, and most of this increase took place after the neonatal stage. Nuclear concentrations of [³H]-T also increased markedly during development in most brain regions except the cerebellar cortex where they declined.

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confidence: 65%

Section: Comparisons Between Fetuses Neonates and Adultsmentioning

confidence: 99%

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Developmental Changes in the Uptake of Testosterone by the Primate Brain

Bonsall

Michael²

1992

Neuroendocrinology

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“…For example, male fetuses have similar levels of aromatase (an enzyme that converts testosterone into estradiol within tissues) in the amygdala as adult males (Clark, MacLusky, & Goldman‐Rakic, 1988; Abdelgadir, Roselli, Choate, & Resko, 1997), although these levels were significantly higher than female fetuses (Roselli & Resko, 1986). Both pre‐ and post‐natally, the amygdala displays higher estradiol and testosterone levels than other neural areas, except for the hypothalamus, and these levels remain stable throughout further development (Sholl, Goy, & Kim, 1989; Sholl & Kim, 1989; Bonsall & Michael, 1992; Michael, Zumpe, & Bonsall, 1992; Abdelgadir et al, 1997).…”

Section: The Amygdalamentioning

confidence: 99%

Non‐human primate models of childhood psychopathology: the promise and the limitations

Machado

Bachevalier

2002

Child Psychology Psychiatry

140

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Although non-human primate models have been used previously to investigate the neurobiology of several sensory and cognitive developmental pathologies, they have been employed only sparingly to study the etiology of childhood psychopathologies for which deficits in social behavior and emotion regulation are major symptoms. Previous investigations of both adult human and non-human primates have indicated that primate social behavior and emotion are regulated by a complex neural network, in which the amygdala and orbital frontal cortex play major roles. Therefore, this review will provide information generated from the study of macaque monkeys regarding the timing of normal social and emotional behavior development, the normal pattern of anatomical and functional maturation of the amygdala and orbital frontal cortex, as well as information regarding the neural and behavioral effects of early perturbations of these two neural structures. We will also highlight 'critical periods' of macaque development, during which major refinements in the behavioral repertoire appear to coincide with significant neural maturation of the amygdala and/or orbital frontal cortex. The identification of these 'critical periods' may allow one to better predict the specific behavioral impairments likely to appear after neonatal damage to one or both of these neural areas at different time points during development. This experimental approach may provide a new and important way to inform and stimulate research on childhood psychopathologies, such as autism, schizophrenia and Williams syndrome, in which the development of normal social skills and emotional regulation is severely perturbed. Finally, the promise and limitations inherent to the use of non-human primate models of childhood psychopathology will be discussed.

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“…This proposition was examined in a study that compared the uptake of [ 3 H]T and its metabolites b}' the brains of castrated male, intact male, and intact, shamoperated female fetuses (Michael, Zumpe, & Bonsall, 1992). Fetal orchidectomy or sham surgery was performed between 110 and 121 days of gestation, after which the fetus was returned to the uterus and pregnancy was maintained for about 1 more week.…”

Section: Developmental Changes In Hormone Uptake By the Primate Brainmentioning

confidence: 99%

Developmental changes in behavior and in steroid uptake by the male and female macaque brain

Michael

Zumpe

1998

Developmental Neuropsychology

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The interaction of testosterone with the brain of the orchidectomized primate fetus

Cited by 6 publications

References 26 publications

Developmental Changes in the Uptake of Testosterone by the Primate Brain

Developmental Changes in the Uptake of Testosterone by the Primate Brain

Non‐human primate models of childhood psychopathology: the promise and the limitations

Developmental changes in behavior and in steroid uptake by the male and female macaque brain

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