The transformation of testosterone into dihydrotestosterone by the brain and the anterior pituitary

Massa, R.; Stupnicka, E.; Kniewald, Zlatko; Martini, L.

doi:10.1016/0022-4731(72)90085-4

Cited by 149 publications

(37 citation statements)

References 6 publications

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“…In vivo, endogenous Sa-dihydrotestosterone enters hypothalamic or pituitary cells from the circulation or is generated in situ from available testosterone (23,50,51). When we infused exogenous Sa-dihydrotestosterone at a rate equal to the daily blood production rate of testosterone in normal men (52,53), there was a two-to threefold elevation of serum levels of Sa-dihydrotestosterone and its major 3a-reduced metabolite, Sa-androstan-3a, 17j3-diol.…”

Section: Discussionmentioning

confidence: 99%

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

Veldhuis¹,

Rogol²,

Samojlik³

et al. 1984

J. Clin. Invest.

193

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As bstract. We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation.When the pure (nonaromatizable) androgen, 5-a-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition ofLH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-1 7,3 did not change significantly, but serum 5a-dihydrotestosterone concentrations increased approximately two-to threefold, with a corresponding increase in levels of its major me- tabolite, 5a-androstan-3a, 17f-diol. In separate experiments, the infusion of estradiol-1 7#3 at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-1 73 levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions.Our observations indicate that, despite the continuous infusion of a dosage of 5a-dihydrotestosterone that significantly suppresses LH pulse frequency, co-administration of an opiate-receptor antagonist effectively reinstates LH pulse frequency to control levels. Moreover, during the infusion of a suppressive dose of estradiol-1 73, opiate receptor blockade significantly augments LH pulse frequency and increases LH peak amplitude to control levels.Thus, the present studies in normal men demonstrate for the first time that the selective inhibitory action of a pure androgen on LH pulse frequency is effectively antagonized by opiate-receptor blockade. This pivotal oW servation indicates that opiatergic and androgen-dependent mechanisms specifically and coordinately control the hypothalamic pulse generator for gonadotropin-re- We conclude that the negative feedback actions of gonadal steroids are integrally coupled to endogenous opiate pathways and that such functional coupling is ultimately expressed at least in part at the level of the hypothalamic pulse generator for GnRH. These observations suggest a model for the proximate regulation of gonadotropin secretion in man, in which the regulatory actions of two major inhibitory systems...

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Section: Discussionmentioning

confidence: 99%

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

Veldhuis¹,

Rogol²,

Samojlik³

et al. 1984

J. Clin. Invest.

193

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“…Thus, in human, as in most other mammalian species, despite the wide structural variation in circulating and intraceliularly formed androgens, only the parent molecule, testoster one, and its 5a-reduced metabolite, 5rx-dihydrotestosterone, bind with high affinity to the androgen receptor in brain tissue. In this context, it is important to recall that the 5a-reduction of testosterone occurs throughout the brain [3,8,24], and thus it is likely that under normal circumstances neurons and other cells within the brain are exposed to 5u-dihydrotestosterone as well as testosterone.…”

Section: Resultsmentioning

confidence: 99%

Androgen Binding Sites in Human Temporal Cortex

et al. 1990

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We have characterized putative androgen receptor binding sites in five separate biopsy samples of human temporal cortex from epilepsy patients using an in vitro exchange assay with soluble fractions and pH]5α-dihydrotestosterone as radioligand. The results revealed highly specific, saturable binding with an apparent affinity constant (K < j) of ∼2 nM with a moderate capacity (B_max) of ∼50 fmol/mg protein. In competition studies, we found that only testosterone and 5α-dihydrotestosterone competed effectively (i.e. at low nanomolar concentrations) for [³H]5α-dihydrotestosterone binding sites. These data indicate the presence of androgen receptors in human cortex that are pharmacologically very similar to that previously described in rodent and infrahuman primate CNS, and suggest the existence of a possible mechanism whereby circulating androgens might influence neuronal events in human cortex.

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“…In the periphery, anterior pituitary and the hypothalamus, testosterone can be converted to dihy drotestosterone (DHT) by the enzyme 5a-reductase and/or can be aromatized to 17(3-estradiol [19][20][21]. Although DHTis about as effective as testosterone in stimulating growth in the prostate, and seminal vesicle [22,23], the metabolite exhibits minimal capacity to maintain or restore copulatory performance in cas trated rats [24].…”

Section: Sexual Behavior and A I3 Da Neuronsmentioning

confidence: 99%

Incertohypothalamic A13 Dopamine Neurons: Effect of Gonadal Steroids on Tyrosine Hydroxylase

Sanghera¹,

Grady²,

Smith

et al. 1991

Neuroendocrinology

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In this study the effect of gonadectomy and steroid treatment on the dorsal component of the incertohypothalamic dopamine system or nucleus A13 was assessed by immunocytochemistry using an antibody raised to tyrosine hydroxylase (TH). A computer graphic system interfaced to a microscope was used to count and measure the diameters of TH-positive neurons and display the data in the three-dimensional space of the nucleus. In males, castration resulted in a dramatic decrease in the reaction product representative of TH. The number of TH-positive cells in the A13 DA nucleus decreased to 25% of intact levels. In females, ovariectomy also caused an impressive loss in the TH-immunostainable material, but this was not indicated by a change in the total number of TH-positive neurons. In both sexes the loss in TH immunostain was confined mainly to the mid-portion of the nucleus. Hormone treatment restored the TH immunostain (cell number and size) to and/or above intact levels in both sexes. These data suggest that A13 TH immunostain is stimulated by gonadal steroids in male and female rats.

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The transformation of testosterone into dihydrotestosterone by the brain and the anterior pituitary

Cited by 149 publications

References 6 publications

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

Androgen Binding Sites in Human Temporal Cortex

Incertohypothalamic A13 Dopamine Neurons: Effect of Gonadal Steroids on Tyrosine Hydroxylase

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