Aromatization of Androstenedione by the Diencephalon

Naftolin, Frederick; Ryan, Kenneth J.; Petro, Zoltan

doi:10.1097/00006254-197204000-00018

Cited by 47 publications

(54 citation statements)

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“…In order to become active, some of the gonadal steroids undergo prior metabolic transformation. Thus testosterone is converted into 5u-dihydrotestosterone in the prostate and the external genitalia, into 3a-5a-androstenediol in the pituitary (Loras et al, 1974;Massa et al, 1975), and into oestrogen in the pituitary and hypothalamus (Naftolin et al, 1971). These hormones also regulate their own secretion by a dual mechanism of positive and negative feedback that is exerted centrally at extra-hypothalamic, hypothalamic and pituitary sites.…”

Section: (C) Peripheral Levelmentioning

confidence: 99%

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Hypothalamic‐pituitary‐gonadal Relationships in Man From Birth to Puberty

Forest

Peretti

Bertrand

1976

Clinical Endocrinology

134

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Gonadal function depends upon activities at various levels. Thus there is: (a) a central level (extra-hypothalamic, hypothalamic, and anterior pituitary); (b) an intermediate level (gonadal and plasma), and (c) a peripheral level consisting of the target organs to which the hormonal message is directed. These determine both the expression of gonadal function (physical, physiological, or psychological) and the feedback regulation of the secretion of gonadotrophins.(a) Central level (i) Extra-hypothalamic centres. The production of LH releasing hormone (LHRH) is affected in the rat, and probably in primates as well, by extra-hypothalamic stimuli coming, in particular, from the amygdala and the hippocampus. Adrenergic regulation exists at this level, noradrenaline having a stimulatory and dopamine an inhibitory effect (Bliss et al., 1972).(ii) Hypothalamic centres. These are localized in particular in the pre-optic area. Immunochemical techniques have demonstrated that LHRH is secreted by neurones of the arcuate nucleus, and released into the capillary plexus proximal to the hypophyseal portal system at the level of the median eminence, thereby reaching the anterior pituitary (Barry & Dubois, 1974;Setalo et al., 1975).(iii) Gonadotrophin secreting cells of the anterior pituitary. These synthesize and secrete the gonadotrophins, LH and FSH, under the influence of LHRH (Schally et al., 1972). The pituitary gonadotrophins stimulate the synthesis and the secretion of the gonadal

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Section: (C) Peripheral Levelmentioning

confidence: 99%

“…Finally, the hypothalamus can be considered as an androgen target organ, as it is capable of selective uptake of labelled testosterone (Abramovich, ! 974), and of aromatization of A4-androstenedione into oestrone (Naftolin et al, 1971).…”

Section: (C) Hypothalamic Control Of Gonadal Function In the Fetusmentioning

confidence: 99%

Hypothalamic‐pituitary‐gonadal Relationships in Man From Birth to Puberty

Forest

Peretti

Bertrand

1976

Clinical Endocrinology

134

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“…Testing this hypothesis, they demonstrated aromatizing enzyme systems capable of metabolizing T to E in the hypothalamus and limbic system of various species, including man (5)(6)(7)(8)(9). The E produced locally from T could then bind to cytoplasmic and nuclear receptors (10)(11)(12)(13) to initiate hormone action.…”

Section: Introductionmentioning

confidence: 99%

“…In men, microgram amounts of E suppress plasma LH levels to the same extent as milligram amounts of T (3)(4). To explain the common actions of these steroids, Naftolin et al postulated that T may be converted into E in the brain (5).…”

Section: Introductionmentioning

confidence: 99%

Is Aromatization of Testosterone to Estradiol Required for Inhibition of Luteinizing Hormone Secretion in Men?

SANrEN¹

1976

Obstetrical & Gynecological Survey

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A B S T R A C T A variety of studies in man and animalsdemonstrate that testosterone (T) is aromatized to estradiol (E) in the hypothalamus and limbic system. These observations suggested the possibility that conversion to E is an absolute requirement for the biologic activity of T on the hypothalamic-pituitary axis. Since this hypothesis implies a common mechanism of action of these two steroids, the demonstration of divergent effects of T and E on luteinizing hormone (LH) secretion would exclude this possibility. To test this hypothesis, the actions of T and E on three separate aspects of LH release (mean LH, pulsatile LH secretion, and responsiveness to LHreleasing hormone [LH-RH]) were contrasted. T and E, infused at two times their respective production rates into normal men, reduced mean LH levels similarly during 6 h of steroid infusion and for 6 h thereafter. However, these steroids exerted different effects on pulsatile secretion. E reduced the amplitude of spontaneous LH pulses from pre-and postinfusion control levels of 75+14 and 68±5.6% (SEM) to 39±5.7%. In contrast, T increased pulse amplitude to 96+14% and decreased pulse frequency from basal levels of 3.4+0.31 to 1.8± 0.31 pulses/6 h.The site of suppressive action was determined by administering 25 lAg of LH-RH to the same men during T and E infusions and during three additional control periods without steroid administration. LH-RH produced similar 170-190% increments in serum LH during the three control periods and during T infusion. In contrast, E markedly blunted (76±31%, P <0.005) the LH response to LH-RH. Under the conditions of acute steroid infusion at doses (utilized in these experiments) pro- ducing similar inhibition of mean LH, E but not T acted directly on the pituitary to diminish LH-RH responsiveness.As further support that androgens can act without conversion to estrogens, the effects of a nonaromatizable androgen, dihydrotestosterone (DHT), on mean LH levels were studied. DHT, infused at the same rate as T, suppressed mean LH to a similar but somewhat greater extent than T. Since T and E produced divergent effects on LH secretion and a nonaromatizable androgen, DHT, suppressed mean LH, aromatization is not a necessary prerequisite for the action of androgens on the hypothalamic-pituitary axis.

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“…Naftolin and co-workers (Naftolin et al, 1971) were the first to describe aromatase expression in the diencephalon. Aromatase is the final enzyme of estradiol synthesis and catalyzes the conversion of testosterone to estradiol.…”

Section: Hippocampal Neurons Synthesize Estradiol Independent Of Gendermentioning

confidence: 99%

Sexual dimorphism in estrogen-induced synaptogenesis in the adult hippocampus

Brandt

Vierk²,

Rune³

2013

Int. J. Dev. Biol.

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It has long been known that estradiol influences synaptic plasticity in the female hippocampus. The density of dendritic spines varies during the estrous cycle and correlates positively with varying levels of estradiol in serum. In accordance, ovariectomy results in a loss of spines that can be rescued by estradiol treatment in animals, suggesting that estradiol originating from the ovaries induces spine formation in the hippocampus. More recent studies point to a role of hippocampusderived estradiol in synaptogenesis in the female hippocampus, rather than of estradiol of ovarian origin. In our studies, we have shown that inhibition of hippocampal estrogen synthesis results in spine synapse loss in female animals and, more importantly, also in ovariectomized animals. Surprisingly, inhibition of local estradiol synthesis had no effect on synapse formation in males, in spite of a similar capacity to synthesize estradiol in male and female hippocampal neurons. In females, neuro-sexual steroid production is promoted by hypothalamic, cyclic GnRH release and likely underlies the estrus cyclicity of spine synapse density in the hippocampus. As a result, peripheral serum concentrations of estradiol determine the amount of estradiol synthesis in the hippocampus. This paradigm may also be true in males. In support of this hypothesis, we found that the content of estradiol in hippocampal tissue is higher in female compared to that in male animals, with low levels of estradiol in serum and tonic and acyclical GnRH release. In summary, our data point to important sex-specific differences in sexual steroid-induced synaptogenesis.

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Aromatization of Androstenedione by the Diencephalon

Cited by 47 publications

References 0 publications

Hypothalamic‐pituitary‐gonadal Relationships in Man From Birth to Puberty

Hypothalamic‐pituitary‐gonadal Relationships in Man From Birth to Puberty

Is Aromatization of Testosterone to Estradiol Required for Inhibition of Luteinizing Hormone Secretion in Men?

Sexual dimorphism in estrogen-induced synaptogenesis in the adult hippocampus

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