Term Castration Research Articles

Behavioral evidence for sex steroids hypersensitivity in castrated male canaries

In seasonally breeding songbirds such as canaries, singing behavior is predominantly under the control of testosterone and its metabolites. Short daylengths in the fall that break photorefractoriness are followed by increasing daylengths in spring that activate singing via both photoperiodic and hormonal mechanisms. However, we observed in a group of castrated male Fife fancy canaries maintained for a long duration under a short day photoperiod a large proportion of subjects that sang at high rates. This singing rate was not correlated with variation in the low circulating concentrations of testosterone. Treatment of these actively singing castrated male canaries with a combination of an aromatase inhibitor (ATD) and an androgen receptor blocker (flutamide) only marginally decreased this singing activity as compared to control untreated birds and did not affect various measures of song quality. The volumes of HVC and of the medial preoptic nucleus (POM) were also unaffected by these treatments but were relatively large and similar to volumes in testosterone-treated males. In contrast, peripheral androgen-sensitive structures such as the cloacal protuberance and syrinx mass were small, similar to what is observed in castrates. Together these data suggest that after a long-term steroid deprivation singing behavior can be activated by very low concentrations of testosterone. Singing normally depends on the activation by testosterone and its metabolites of multiple downstream neurochemical systems such as catecholamines, nonapeptides or opioids. These transmitter systems might become hypersensitive to steroid action after long term castration as they probably are at the end of winter during the annual cycle in seasonally breeding temperate zone species.

“Castration Anxiety” Revisited: Especially “Female Castration Anxiety”

ABSTRACTI find the term castration anxiety a still relevant and important key body fearful fantasy in males, especially expressing fear of the father; as is female castration anxiety an equivalent key fear of the ablation of the sexual and reproductive organs of females, especially by the avenging mother. Freud’s and his followers’ version of the female anxiety, however, has repetitively been shown to be askew since the 1930s, yet it keeps appearing again, as if still worthy of serious argument. To demonstrate its utter blindness to an emotional or imaginative appreciation of female body reproductive functioning, a detailed critique is offered of the once classic paper, “The Body as Phallus” by Bertram Lewin (1933). I recommend that a straightforward sense of female castration is helpful in exploring female body anxieties as a more defined bodily referent than can be encompassed by separation anxieties that are currently more popular.

Castration-Resistant Prostate Cancer: Descriptive Yet Pejorative?

TO THE EDITOR: The euphemistic term castration-resistant prostate cancer (CRPC) has slowly entered the everyday lexicon of those who study and treat prostate cancer. Ahmann and Crawford utilized this term in 1987. Emanating from what used to be called hormonerefractory prostate cancer and/or androgen-independent prostate cancer, this CRPC consensus definition was first formally reintroduced at a 2005 ODAC discussion on prostate cancer trial end points. Subsequently, in 2008, it was specifically defined in a Prostate Cancer Working Group Guidelines report, published in Journal of Clinical Oncology. At that time, Scher et al recognized that despite medical or surgical castration, prostate cancers were still sensitive to subcastrate levels of androgens, either emanating from the adrenal cortex or from prostate cancer cells themselves (with direct intracrine activation of the androgen receptor cascade). However, there have been some concerns expressed by clinicians, and more importantly by patients themselves, that the term castration implies some sort of testicular removal, which has a negative connotation for many men who have this disease. Hormone-refractory prostate cancer and androgen-independent prostate cancer did not have this perceived stigma, but in contrast, they have proven to be considerably inaccurate, as secondgeneration androgen deprivation therapy clinical trials are beginning to demonstrate. Therefore, we would like to propose that a term such as endocrineresistant prostate cancer may be a better description to utilize with our colleagues and patients. It is both accurate and less emotionally charged. Seen in this fashion, it gives us in the field, as well as our patients, a clearer way to view therapeutic options (which will increase significantly in the years to come). Therapeutically, if patients knew their disease was either endocrine sensitive or endocrine resistant, potentially approvable agents like Abiraterone, MDV-3100, and even estrogenic compounds could be clearly delineated from the evolving nonhormonal options that are also coming down the pike, like immunotherapy, targeted agents, and newer chemotherapies.

Quantification of insulin-like growth factor-1 (IGF-1) mRNA: development and validation of an internally standardised competitive reverse transcription-polymerase chain reaction.

To investigate the role of local IGF-1 mRNA expression in various tissues, we developed and validated a method which allows for a specific, sensitive and reliable quantification of IGF-1 mRNA: an internally standardised Reverse Transcription-Polymerase Chain Reaction (RT-PCR). A synthetic competitive template IGF-I standard cRNA (IGF-1 cRNA) was designed, which contains the same flanking primer sequences used to amplify the wild type IGF-1 mRNA, but differs by 56 bp in length. To obtain the IGF-1 mRNA concentration present in tissue RNA samples, series of 250 ng total-RNA were spiked with three known quantities of the standard IGF-1 cRNA, incubated for competitive RT-PCR reactions and the two amplificates obtained (184 bp from IGF-1 cRNA and 240 bp from the wild type IGF-I mRNA) were subsequently separated and quantified by HPLC-UV. For every individual tissue RNA sample, the ratio R (R = competitor PCR product / wild type PCR product) was plotted against the number of starting molecules of the competitor IGF-1 cRNA. The initial amount of IGF-1 mRNA present in the sample can then be read off where R = 1. The validated assay had a detection limit of 1600 IGF-1 cRNA molecules/reaction, the intra-assay variation was 7.4% (n = 5) and linearity (r = 0.997) was given between 140 ng to 840 ng total-RNA input. The present method was first applied to study the effect of long term castration on the IGF-1 expression rates in bovine tissues. The hepatic IGF-1 mRNA concentrations were well correlated (r = 0.81) with the plasma concentrations as quantified by RIA and were higher in intact than in castrated animals. In two skeletal muscles (m. splenius and m. gastrocnemius) IGF-1 mRNA concentrations were 20- and 35- times lower than in liver, respectively, without any differences between steers and bulls. In bulls, the IGF-1 mRNA expression was higher in m. splenius (p < 0.01) than m. gastrocnemius, indicating that locally produced IGF-1 might be important for sexually dimorphic muscle growth patterns.

Long-Term Consequences of Castration in Men: Lessons from the Skoptzy and the Eunuchs of the Chinese and Ottoman Courts

Castration of men and males of other species was almost certainly the first experiment in endocrinology (if not in zoology), and the literature on the subject is vast. Indeed, the Cumming Manuscript Collection of the New York Academy of Medicine Library contains more than 1200 references, abstracts, and documents concerning the early history of human castration (1). In antiquity the procedure was performed for several reasons, including as punishment for prisoners of war (2), and by the time of Aristotle in the fourth century BC the physiological consequences of male castration were understood with remarkable exactitude (3). “Some animals change their form and character, not only at certain ages and at certain seasons, but in consequence of being castrated; and all animals possessed of testicles may be submitted to this operation. Birds have their testicles inside, and oviparous quadrupeds close to the loins; and of viviparous animals that walk some have them inside, and most have them outside, but all have them at the lower end of the belly. Birds are castrated at the rump at the part where the two sexes unite in copulation. If you burn this twice or thrice with hot irons, then, if the bird be full-grown, his crest grows sallow, he ceases to crow, and forgoes sexual activity; but if you castrate the bird when young, none of these male attributes or propensities will come to him as he grows up. The case is the same with men; if you mutilate them in boyhood, the latergrowing hair never comes, and the voice never changes but remains high-pitched; if they be mutilated in early manhood, the later growth of hair quit them except the growth on the groin, and that diminishes, but does not entirely depart. The congenital growth of hair never falls out, for a eunuch never goes bald. In the case of all castrated or mutilated male quadrupeds the voice changes to the feminine voice. . . All animals, if operated on when they are young, become bigger and better looking than their unmutilated fellows; if they be mutilated when full-grown, they do not take on any increase of size. If stags be mutilated when, by reason of their age, they have as yet no horns, they never grow horns at all; if they be mutilated when they have horns, the horns remain unchanged in size, and the animal does not lose them. . . As a general rule, mutilated animals grow to a greater length than the unmutilated (3).” In contrast to the rapidity and sophistication of the early advances, studies of the physiological effects of castration in more recent times have been relatively limited (presumably because fewer castrated men are available for study), and most studies of androgen deficiency focus on hypogonadal states rather than castration (4). However, in the 1940s, Hamilton and his colleagues did pioneering work in the United States on mentally deficient men who were castrated as a consequence of eugenics laws, quantifying the effects on skeletal development, hemoglobin production, and metabolism (5), and Bremer subsequently defined the relation between testicular secretions and male sexual drive and function in men who were castrated in Norway because of sexual offenses (6). Most studies of castration in men have involved relatively short term experiences (usually men who had been castrated for less than a decade), but in the 20th century the effects of long term castration have been studied in three groups of men: the Skoptzy and the court eunuchs of the Chinese and Ottoman empires (Table 1). According to Penzer (7) three varieties of eunuchs were recognized in antiquity: 1) castrati, clean-cut, both penis and testicles were removed; 2) spadones, testicles only were removed; and 3) thlibiae, testicles were bruised and/or crushed. The three groups of eunuchs under consideration in this review fall into the castrati category.

Effects of testosterone on neuronal nitric oxide synthase and tyrosine hydroxylase

Male rat copulatory ability decreases dramatically following castration. This may be due in part to the impairment of medial preoptic area (MPOA) dopamine (DA) release. Previous studies showed that extracellular DA levels in the MPOA of castrates were lower than in intact males, both during basal conditions and in the presence of a receptive female. However, tissue levels of DA in the MPOA were higher in castrates than in intact males, suggesting that DA synthesis may be normal or increased in castrates, but that release may be compromised. The current study found that neither long term (2 months) nor short term (2 weeks) castration had any effect on the number of neurons in the DA A 14 area that were immunoreactive (ir) for tyrosine hydroxylase (TH), the rate limiting enzyme for DA synthesis. Therefore, castration may not affect DA synthesis in the MPOA. Tissue levels of neurotransmitter reflect release, as well as synthesis. We previously reported that nitric oxide (NO) may increase DA release in the MPOA. The present study tested whether castration affected the number of NO producing cells in the MPOA. Long term, but not short term, castration significantly decreased the number of NADPH-d (nicotinamide adenine dinucleotide phosphate diaphorase) positive neurons and brain nitric oxide synthase immunoreactive (bNOS-ir) neurons in the medial preoptic nucleus (MPN). This suggests that in gonadally intact animals testosterone may activate NOS, which increases the production of NO. Long or short term castration had no effect on the numbers of bNOS-ir neurons in the paraventricular nucleus (PVN) or medial amygdala. However, short term castration decreased bNOS-ir neurons in the bed nucleus of stria terminalis (BNST). Thus, one means by which testosterone promotes male sexual behavior may be by increasing production of NO in the MPOA, which increases local DA release.

Septal arginine vasopressin (AVP) receptor regulation in rats depleted of septal AVP following long-term castration

Arginine vasopressin (AVP) causes severe motor disturbances, including barrel rotations and myotonic/myoclonic convulsions, following repeated injections into either a lateral cerebral ventricle or the ventral septal area (VSA) of the rat brain. Because the AVP content of the rat septal area has been shown to be virtually eliminated following long-term castration, and because removal of a receptor ligand typically results in receptor upregulation and behavioral supersensitivity to the ligand, we tested the hypothesis that long-term castrated rats may be supersensitive to the motor actions caused by centrally injected AVP and may have upregulated septal AVP receptors. In these experiments, adult male Wistar rats were used 5 months after castration or, as controls, after sham castration. The effectiveness of long-term castration in eliminating AVP content of the VSA was indicated by the observation that a priming hypertonic saline stimulus (known to induce the central release of AVP and sensitize the rat brain) sensitized the brains of sham control rats but not of the castrated rats to the motor actions of a subsequent intracerbroventricular injection of AVP. The motor actions of centrally injected AVP, as well as septal AVP receptor characteristics (number and affinity), and AVP-stimulated phosphoinositide (PI) hydrolysis were then investigated in long-term castrated and sham control rats. Motor disturbances induced by either a first or a second injection of AVP were not greater in long-term castrated rats than in sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of Androgen Receptor Protein and mRNA Concentrations by Androgens in Rat Ventral Prostate and Seminal Vesicles and in Human Hepatoma Cells

The effects of androgen withdrawal and replacement on the concentrations of androgen receptor (AR) protein and AR mRNA were investigated in rat ventral prostate and seminal vesicles and in cultured human hepatoma (HepG2) cells. AR mRNA concentrations were determined by Northern blotting with single stranded AR cRNA as the hybridization probe, whereas antibodies raised against two synthetic 17-amino acid long peptides corresponding to the N-terminal and steroid-binding regions of the AR were employed in immunological receptor assays. AR mRNA levels in both prostate and seminal vesicles increased about 2-fold within 24 h after castration and continued to rise within the next 48 h to values that were 9- to 11-fold higher than those in intact controls. Administration of pharmacological doses of testosterone (400 micrograms steroid/day) to 1-day castrated animals for 24-48 h brought about a decrease in AR mRNA levels in accessory sex organs to levels in intact controls. Similar results were obtained in cultured HepG2 cells where a switch to serum- and steroid-free medium elicited a rapid increase (approximately 4-fold in 10 h) in the AR mRNA level, which was prevented by inclusion of 10(-7) M testosterone in culture medium. Similar, but quantitatively less marked, changes occurred in the AR protein concentration in prostate, seminal vesicles, and HepG2 cells, as determined by immunoblotting using antibodies against AR peptides. In addition, immunohistochemical studies showed that AR is a nuclear protein of the prostatic epithelial cells in both intact and castrated rats, and suggested that short term castration increases the concentration of nuclear AR in the prostate. Taken together, these data indicate that androgens down-regulate the concentration of AR protein and AR mRNA in a variety of target tissues.

Androgen and estrogen effects on protein synthesis by the adult rabbit epididymis.

The effects of castration and hormone replacement on [35S]methionine incorporation into newly synthesized proteins by the adult rabbit epididymis were studied in vitro. The proteins were analyzed using two-dimensional polyacrylamide gel electrophoresis. Short term (4-day) castration resulted in a few changes in the pattern of radiolabeled proteins observed in the caput, but no effect was seen in the corpus or cauda. The changes in the caput could be reversed if the samples were incubated with testosterone. The epididymis of short term castrates failed to respond to exogenous estradiol. Long term castration (4-6 weeks) resulted in changes in protein synthesis among all three epididymal segments. Short term (4-h) incubation with testosterone restored the pattern of proteins secreted by the caput and cauda to that in intact rabbits. Short term incubation with estradiol did not restore the pattern of radiolabeled secreted proteins, but it did slightly intensify a 28K protein (pI 5.2) that was present in the caput and cauda of castrated animals. No clear-cut effect of the hormones on proteins secreted by the corpus was observed. Short term incubation with testosterone or estradiol restored the patterns of tissue proteins synthesized by the caput and corpus of castrated rabbits to that in intact animals. In the cauda, estradiol also enhanced the presence of a small group of high mol wt proteins present in the control castrate sample, while testosterone inhibited these proteins. This group of proteins was absent in cauda tissue samples from intact rabbits.

Synaptology of luteinizing hormone-releasing hormone neurons in the preoptic area of the male rat: Effects of gonadectomy

Ultrastructural analysis of the synaptic input to luteinizing hormone-releasing hormone neurons has previously shown that in male rats these cells acquire an increased density of innervation with increasing age [Witkin J. W. (1987) Neuroscience 22, 1003–1013]. To determine if this aging phenomenon might be due to changes in the steroid environment, we examined luteinizing hormone-releasing hormone neurons, using methods identical to the earlier study, in sham operated and 1 day and 4 week castrated male rats. The density of synaptic input to luteinizing hormone-releasing hormone neurons did not vary among the three experimental groups. Furthermore, there were no differences in the relative numbers of various morphological categories of synaptic boutons (characterized by vesicle type: clear vs dense and round vs pleomorphic) among the groups. Long term castration did result in a slight decrease in immunocytochemically detectable luteinizing hormone-releasing hormone neuron numbers. These results suggest that gonadal steroid deprivation does not alter the total density or morphological characteristics of synaptic input to the luteinizing hormone-releasing hormone neuron in the male rat.

Androgen regulation of muscle fiber type in the sexually dimorphic larynx of Xenopus laevis

We used histochemical techniques [assays for adenine triphosphatase (ATPase) and succinate dehydrogenase (SDHase) activity] to identify muscle fiber types in the larynx of Xenopus laevis. Male muscle is made up of one fiber type, medium-sized fibers (approximately 9 microns2) that stain lightly for acid-stable ATPase and intensely for SDHase activity. In contrast, the female has 3 fiber types: small fibers (approximately 6 microns2) that stain intensely for ATPase and SDHase, medium-sized fibers (approximately 13 microns2) with moderate staining for ATPase and dark staining for SDHase, and large fibers (approximately 15 microns2) with little SDHase or ATPase activity. Long-term castration (6 months) has no effect on histochemical staining of adult male fibers. Long-term testosterone treatment (5 months) increases the proportion of medium-sized, moderately staining fibers in adult females, and reduces the proportion of both the small, darkly staining fibers and the large, lightly staining fibers. At metamorphosis, both males and females have 3 fiber types whose ATPase activity is similar to that of the adult female. However, no SDHase activity is observed. Treatment of juveniles for 3 weeks with testosterone results in nearly complete masculinization of muscle fibers, as judged by increased cross-sectional area, homogeneous ATPase staining, and a marked increase in SDHase activity. Thus, juvenile muscle is considerably more responsive to testosterone than is adult female muscle. We propose that the uniform metabolic properties of male laryngeal muscle contribute to the production of the rapid (66 Hz) mate call vocalizations characteristic of this species. Further, our results suggest that androgens direct the masculinization of laryngeal muscle fibers during postmetamorphic development.

Hypercholesterolaemia, hypotriacylglycerolaemia and increased lipoprotein lipase activity following orchidectomy in rats.

Plasma lipoproteins, faecal cholesterol excretion, and activities of lecithin: cholesterol acyltransferase (LCAT) hepatic lipase (HL), and lipoprotein lipase (LPL) were determined in castrated rats, in rats treated with testosterone propionate after castration, and in sham-operated controls. Compared to control rats, whole-plasma total cholesterol (TC) rose, and triacylglycerols (TG) fell in castrated rats, but were normalized by androgen substitution. VLDL components tended to be reduced, whereas HDL2 components rose following castration. In general, testosterone substitution normalized the alterations induced by castration. Adipose tissue LPL was higher in castrated rats than in control rats, whereas activities of HL and LCAT were not significantly affected by the treatments. Hepatic cholesterol concentration, and faecal excretion of cholesterol and bile acids were not significantly altered by the treatments. Considering all 3 groups together, there was a significant positive correlation between the concentration of plasma cholesterol and cholesterol in liver, between plasma HDL2-cholesteryl esters and hepatic cholesterol, and also between HL and faecal cholesterol excretion. The results suggest that short term castration of rats causes increased levels of lipoprotein lipase and thereby brings about a lowering of VLDL and an increased concentration of LDL and HDL2. These effects are reflected in hypotriacylglycerolaemia and hypercholesterolaemia.

Histochemical studies on genetical control of hormonal enzyme inducibility in the mouse. VI. Effects of short term castration.

The regional histology and esterase activity of the mouse epididymis after 24, 48, and 72 hr castration is reported. Differential sensitivity to androgen deprivation among the various epithelial cell types is described, allowing of positive identification of the cell types previously observed to survive long-term castration. The possibility of an androgen binding protein, as described in the rat and rabbit, is suggested on morphological grounds. The epididymal body appears to contain a class of highly androgen sensitive cells that degenerate rapidly following castration and a second class that survive from which regeneration occurs on testosterone replacement.

Regulation of the androgen and glucocorticoid receptors in rat and mouse skeletal muscle cytosol.

Using a charcoal technique, we determined the relative binding affinity of some anabolic compounds for the androgen and glucocorticoid receptors in cytosol from rat skeletal muscle. Only a few of the compounds analyzed competed for the receptor-binding sites. The androgen and glucocorticoid receptors were analyzed in rat and mouse skeletal muscle cytosols by Scatchard analysis. In rats grouped according to sex and age, the cytosolic protein content was about the same in all groups, but the DNA content decreased with increased weight of the animal regardless of sex (male, female, or castrated male). The glucocorticoid receptor did not differ in concentration (2-3 pmol/g tissue) or ligand affinity (Kd, 10-40 nM) among the groups, but the androgen receptor concentration decreased with increased weight and age of the animals, more in the case of males than in the case of females or castrates. The Kd for the androgen receptor increased with age in males but was constantly about 0.2 nM for castrates or females. In adult intact rats, the androgen and glucocorticoid receptor concentrations in muscle cytosol from females were about 100 and 3000 fmol/g tissue, respectively, the corresponding values for males being about 50 and 2000 fmol/g tissue, respectively. Short term castration or adrenalectomy increased the concentration of and ligand affinity for the androgen and glucocorticoid receptors, respectively. After long term castration of male rats, the concentration of both receptors increased during 5 weeks to about the female level, only to decrease later. Neonatally castrated male rats had about the same androgen receptor concentrations and Kd values as female rats. Female mice had higher androgen receptor concentrations (approximately 700 fmol/g tissue) than rats. Intact male mice had about 200 fmol androgen receptor-binding sites/g tissue, and the same amount was found in mice bearing the testicular feminization (Tfm) mutant gene. In summary, the concentrations of androgen and glucocorticoid receptors in rat skeletal muscle are regulated at least by the testes. The presence of androgen receptors in skeletal muscle from Tfm mice is surprising and may motivate a reinvestigation of the regulation of androgen receptors in Tfm animals.

Photoperiodic control of androgen metabolism and binding in androgen target organs of hamsters ( Phodopus sungorus)

Male Dshungarian dwarf hamsters ( Phodopus sungorus, Pallas 1776) aged 90 ± 7 days were used throughout the study. They were kept either under long photophase days of 16L:8D (group L) or under short photophase days of 8L:16D (group S). Testes and prostate weight and total radioactivity uptake into various organs 30 min. after intracardial injection of [ 3H]-testosterone ([ 3H]−T) were determined. Photoperiodical changes in the action of steroids were investigated by the determination of the [ 3H]−T metabolite pattern in vivo, and by in vitro studies on the available androgen receptor of prostate cytosol. The S-group reduced the weight of the testes to 3% and that of the prostate and seminal vesicles to 10% of the L-group values. The decrease in the weight of the accessory sex organs was accompanied by a dramatic increase in the radioactivity uptake relative to plasma. The plasma of S-hamsters retained less radioactivity than that of L-hamsters. The metabolite pattern of [ 3H]-T in prostate and seminal vesicles in vivo changed towards increased inactivation with less 5α-dihydrotestosterone and more steroids of high polarity formed. An increase in the concentration of available binding sites of the prostate cytosol androgen receptor was observed in S-hamsters when compared to the L-group. Short term castration (16h) increased the receptor in both, L- and S-hamsters, while long term castration (7 days) lowered the receptor by 60% compared toshort term castrated hamsters. The data indicate, that a photoperiodic control of androgen action exists on the level of the target organs, which is assisted by peripheral changes of androgen metabolism, as reflected in plasma, which are not directly controlled by the hypophyseal-gonadal feed back system. The peripheral changes lead to a higher elimination and inactivation of plasma T under short photoperiods. Furthermore, in the target organs also a higher inactivation and a lower formation of biologically active metabolites suppress the biological action of the remaining active androgen. The decreasing androgen levels are also accompanied by increasing available cytosolic androgen receptor concentrations. The decrease of receptor after long term castration suggests that the regressed testes are involved in the maintainance of the androgen receptor and of androgen responsiveness.

Testosterone and UVL‐B stimulation of epidermal melanocytes in rat scrotal skin

The effects of UVL-B and/or testosterone replacemnt therapy are compared in normal and castrated rats in order to determine whether testosterone is required for UVL-B (290-315 nm) stimulation of melanogenesis in the testosterone-dependent epidermal melanocyte system of the scrotal skin of black Long Evans rats. Testosterone is not a prerequisite for UVL-B stimulation of melanocytes as in both castrates and normal animals the melanocytes respond to UVL-B by increases in size, length and number of dendrites (dendriticness), and tyrosinase activity (intensity of Dopa reaction). Addition of testosterone to castrates does enhance the effects of UVL-B. However, UVL-B with or without testosterone cannot maintain normal melanogenesis in rats irradiated immediately after castration nor can it restore normal melanogenesis following long term castration. Bth the amount of UVL nergy/exposure and the number of exposures are important variables in stimulation of the epidermal melanocytes. Administration of a dose of UVL-B to castrates in a single exposure is ineffective, while the same overall dose spread over several exposures increases the size and dendriticness of melanocytes. Testosterone and UVL-B act synergistically in affecting melanogenesis although neither singly nor in combination are they able to fully restore normal melanogenesis.

GABA and gonadal hormones

Summary The effects of alterations in the androgen status of male rats was investigated with respect to the possible involvement of hormones in GABAergic regulation. The methods used to study this hormone-GABA relationship revealed: (1) Long term castration of rats caused a decrease in GABA concentration in the amygdala and septal area, while a slight but consistent increase in concentration was found in the midbrain. (2) Testosterone substitution was effective in reversing this decrease in GABA associated with castration, but had no discriminable effect on the midbrain steady state concentrations. (3) Estradiol substitution reversed the reduction in GABA found with castration and further increased GABA concentrations in the midbrain. (4) Dihydrotestosterone had no effect on amygdaloid or septal concentrations but was effective in reducing GABA concentration in the midbrain. (5) After GABA transaminase inhibition by aminooxyacetic acid the concentration of GABA in castrated animals was lower compared to sham animals in all 3 brain regions. Testosterone reversed this reduction in all areas. The findings suggest that castration causes a decrease in GABA synthesis in several brain regions and that this is an effect of a reduction in circulating testosterone and/or estradiol concentrations. Castration may also cause a decrease in turnover of GABA in the midbrain which is reversed by dihydrotestosterone and/or testosterone.