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The riddle of femininity: the interplay of primary femininity and the castration complex in analytic listening.

This study elucidates the application of an analytic attitude to questions of gender and sexuality. The paper reports on a study group's exploration of the relative heuristic use of two important organising concepts in analytic work with female analysands: primary feminity and the phallic castration complex. A tendency to cling to one position over the other skews analytic listening. Two cases are presented of women struggling to consolidate positive feminine identifications and, to that end, working through conflicting feminine identifications and defences against a resolution of the awareness of gender differences. Analytic listening requires a view of each psychic construction as a layer to be understood in its own right yet as a cloak soon to reveal the next layer--a different construction. The study includes observations on perverse fantasies in women.

Adult↗

Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy.

Transgenic models of neurodegenerative disease have proved uniquely powerful for delineating pathways of neuronal dysfunction and cell death. We have developed a transgenic model of the polyglutamine disease spinal and bulbar muscular atrophy (SBMA), an adult-onset, slowly progressive motor neuron disease caused by polyglutamine expansion in the androgen receptor (AR). Mice bearing a human AR with 112 glutamines reproduce many aspects of SBMA, including slowly progressive, gender-specific motor deficits, and neuronal intranuclear inclusions. Despite substantial motor deficits in male AR112Q mice, no motor neuron loss was observed, indicating that neuronal dysfunction, rather than neuronal death, is central to disease. Moreover, reduced levels of unphosphorylated neurofilament heavy chain (NF-H) were observed in motor neurons, suggesting a role for NF-H in SBMA neuronal dysfunction. The elimination of androgens by surgical castration of severely affected, aged 112Q male mice partially restored motor function as well as NF-H levels. These data suggest that hormone-based therapies designed to treat SBMA patients, even with advanced disease, are likely to be effective.

Animals↗

Gonad-gonadotrope interactions: plasma gonadotrophin levels and tumour induction in long-term castrated rats.

The patterns of gonadotrophin secretion in intact controls and in male and female rats castrated for up to 36 months were established utilizing specific radioimmunoassay methods. Plasma LH increased 14-16 fold and FSH rose 4-8 fold in rats of either sex in the first 30 day interval showed an additional 76% increase of LH in both sexes and increases in FSH of 32 and 61% in males and females, respectively. These levels were maintained for an additional 34 months. The number of hypophyseal gonadotrophin containing cells, studied by immunohistochemical localization techniques, increased following gonad removal in a pattern similar to that for the circulating hormones. Development of gonadotrophin secreting concentrations which suggests that the gonadotropes are uniquely resistant to tumourogenesis unlike mammotropes, thyrotropes, and corticotropes.

Animals↗

Cyclophenil, a non-steroidal compound with a higher central than peripheral oestrogenic activity: study of its effects on uterine growth and on some central parameters in castrated female rats.

The oestrogenic activity of cyclophenil, a non-steroidal compound which has structural analogies with both stilbene and triphenylethylene, has been reevaluated utilizing both central and peripheral parameters. The central parameters considered were LH, FSH, prolactin secretion and two enzymatic systems known to be oestrogen-sensitive: hypophyseal 5alpha-reductase and hypothalamic aromatase. The uterine growth test was used to determine oestrogenic peripheral activity. The compound was administered at various doses in comparison with oestradiol benzoate (EB) to long-term castrated female rats. Cyclophenil has an activity 1/8110 times that of EB on uterine growth, and 1/1660 and 1/550 times that of EB in inhibiting LH and FSH, respectively. The hypophyseal 5 alpha-reductase (expressed as DHT formation) was inhibited 1710 times less by cyclophenil than by EB. The other parameters considered were unsuitable to provide a statistically reliable estimate of the potency ratios between the two compounds. The data show that cyclophenil is an oestrogenic compound with peculiar characteristics. This substance is more effective in expressing its oestrogenic activity in central structures than in the peripheral ones.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Growth and bone haemodynamic responses to castration in male rats. Reversibility by testosterone.

Orchidectomy in postpubertal 55 day old rats, compared to sham-operated controls, led beyond 2 months to a decrease in body weight (87% of controls by 120 d), tibial length (97% of controls) and in tibial calcium content (85% of controls). Bone plasma flow increased three times to reach a peak at 31 days; it was decreased but no significantly at 86 and 120 days. The number of osteoclasts was maximal at 51 days (X 2.3) and was still elevated at 120 days. The calcium accretion rate increased briefly at 31 days (110% of controls) and was diminished at 86 and 120 days (78% of controls). The initial 'physiological' changes in the tibia occurred before any weight change and might be directly due to the lack of androgens. They can be interpreted as inducing the conditions for enhanced bone resorption. Testosterone replacement therapy, initiated after the initial haemodynamic response, inhibited the negative effect of castration on bone growth.

Age Factors↗

Inhibition of testosterone 5alpha-reductase activity and growth of accessory sex tissues in castrated male mice.

The steroid 4-androsten-3-one-17beta-carboxylic acid (17betaC) reduced the growth-promoting actions of testosterone, but not those of DHT in accessory sex tissues of castrated mice. The 5alpha-reduction of testosterone to DHT in these tissues was also reduced by 17betaC treatment, suggesting that DHT formation is a required step in the mechanism of action of testosterone.

5-alpha Reductase Inhibitors↗

Plasma concentrations of FSH and LH in entire and castrated prepubertal bull calves treated with Gn-RH.

In bulls there was no increase in plasma FSH and only a small increase in LH over the first 14 weeks of age. In steers (castrated) plasma LH and FSH were unchanged for the first 3 weeks but increased significantly at 7 and 14 weeks. After 100 micrograms Gn-RH, LH release in bulls was minimal until 7 and 14 weeks and there was no comparable rise for FSH. LH and FSH responded to Gn-RH throughout the trial in the steers. The neonatal calf testes selectively inhibited the release of FSH from the pituitary even when challenged with Gn-RH.

Animals↗

Antiandrogenic effect of delta-9-tetrahydrocannabinol in adult castrated rats.

In ventral prostate tissues of adult castrated rats, delta-9-tetrahydrocannabinol (THC) at 10 mg/kg for 7 days counteracted the testosterone-induced changes of (i) DNA, RNA and protein content, (ii) the tartrate-insensitive form of acid phosphatase, and (iii) the isoenzyme variant of acid phosphatase associated with the secretory type enzyme. These results indicate that THC acts anti-androgenically and directly at the level of male accessory sex organs.

Acid Phosphatase↗

Influence of incubation conditions, tunicamycin and castration on incorporation of [3H]mannose and [3H]fucose into rat epididymal glycoproteins in vitro.

The incorporation of radioactive mannose and fucose into secretory glycoproteins by rat epididymal tissue was studied using tissue pieces in vitro. The appearance of radioactive macromolecular products in the medium occurred after a lag phase of 2 h with radioactive mannose, but with radioactive fucose the lag phase was only 15 min. Preincubation of tissue for 2 h before the addition of radioactive mannose increased the subsequent rate of incorporation by reducing the lag phase from 2 to 1 h. Tunicamycin reduced the incorporation of radioactive mannose and fucose into macromolecular products to approximately 15 and 50% of normal in the caput and cauda respectively; maximum inhibition required 10 micrograms tunicamycin/ml in the caput and 2 micrograms/ml in the cauda. Reduction of radioactive sugar incorporation by tunicamycin did not result in qualitative changes in the profile of the radioactive glycoproteins that were secreted. However, immunoprecipitation of proteins D and E from incubations with radioactive methionine or mannose revealed that tunicamycin caused these proteins to be synthesized and secreted in a non-glycosylated form. Prior castration of animals reduced the incorporation of radioactive mannose and fucose, and qualitative changes in the profiles of secreted radioactive glycoproteins were apparent.

Animals↗

Behavioural and morphological effects of 5 alpha-dihydrotestosterone and oestradiol-17 beta in the prepubertally castrated boar.

Three groups of 5 prepubertally castrated boars received twice weekly subcutaneous injections from 16 to 28 weeks of age of 5 alpha-dihydrotestosterone propionate (1 mg/kg), oestradiol-17 beta dipropionate (0.1 mg/kg), or a combination of the two steroids. The pigs were tested each week for sexual behaviour with an oestrogen-treated ovariectomized gilt. 5 alpha-Dihydrotestosterone did not induce copulatory behaviour whereas oestradiol initiated mounting, although this behaviour was not maintained. However, the combined hormonal treatment induced the full pattern of copulation, including ejaculation, in 4/5 pigs. Oestrogen-treated animals also showed champing and salivation. None of the pigs treated with 5 alpha-dihydrotestosterone showed lordosis when exposed to a mature boar. Increases in the size of the penis, the ischio- and bulbocavernosus muscles, seminal vesicles and bulbourethral glands were produced by 5 alpha-dihydrotestosterone, and, with the exception of the penis, this hypertrophy was further enhanced by additional treatment with oestradiol. Increases in the weight of the prostate and muscular urethra were due mainly to the effects of oestrogen; this steroid caused extensive development of fibromuscular tissue and also increased mammary teat length. In the submaxillary salivary glands, synergism between 5 alpha-dihydrotestosterone and oestradiol resulted in hypertrophy of the serous cells.

Animals↗

Effects of Eurycoma longifolia Jack (Tongkat Ali) on the initiation of sexual performance of inexperienced castrated male rats.

We studied the effects of Eurycoma longifolia Jack, commonly known as Tongkat Ali in Malaysia, on the initiation of sexual performance and the weights of sexual accessories in inexperienced castrated male rats. The doses of 200, 400 and 800 mg/kg body weight, which were extracted from E. longifolia Jack, were orally administered to the rats twice daily for 10 days prior to the tests and continued throughout the test period. Testosterone was used as a positive control after injecting 15 mg/kg daily subcutaneously for 32 days. Results showed that E. longifolia Jack produced a dose-dependent increase in sexual performance of the treated animals, but the E. longifolia Jack groups showed lower sexual performance in mounting, intromission and ejaculation than the testosterone group. Further results also showed that E. longifolia Jack promoted the growth of both ventral prostate and seminal vesicles as compared with the control, but the growth of sexual accessories at 800 mg/kg of butanol, methanol, water and chloroform fractions of E. longifolia Jack was less than that of testosterone treated group. The present study therefore gives further evidence of the folkuse of E. longifolia as an aphrodisiac.

Animals↗

Effects of castration and gonadal steroids on serum luteinizing hormone and prolactin in old and young rats.

Changes in serum LH and prolactin concentrations in response to bilateral gonadectomy and gonadal steroid replacement were measured in mature young (4-6 months) and old (23-30 months) female and male Long-Evans rats. On day 13 after gonadectomy, female rats were injected with oestradiol benzoate (OB) and male rats with testosterone propionate (TP) for a period of 12 days. They were then permitted a recovery period of 6 weeks. Serum prolactin and LH concentrations were measured by radioimmunassay in single blood samples taken at various intervals before and after gonadectomy and during and after steroid treatment. Serum LH levels were about the same in intact young old female rats, but after ovariectomy LH rose several fold higher in young than in old remale rats. In male rats, after orchidetomy the increase in serum LH was greater in young than in old rats. Oestradiol benzoate and TP injections into female and male young and old rats produced variable effects on LH release. Serum prolactin concentrations were approximately six times higher in old intact than in young intact female rats, and after ovariectomy showed a much greater percentage reduction in old than in young female rats. Administration OB produced a greater absolute increase in serum prolactin in old than in young female rats. Serum prolactin values were about the same in old and young male rats, and the effects of castration and TP administration on serum prolactin were not markedly different in the two age groups. These results indicate that old female and male rats are less capable of releasing LH than young rats of both sexes, but old females release more prolactin than young females.

Aging↗

Sexual behaviour in castrated rabbits treated with testosterone, oestradiol, dihydrotestosterone or oestradiol in combination with dihydrotestosterone.

Sexual behaviour and the function of the accessory sexual glands were studied in castrated rabbits injected with testosterone benzoate (TB), oestradiol benzoate (OEB), dihydrotestosterone benzoate (DHTB) or OEB in combination with DHTB. Testosterone benzoate (1 mg daily for 90 days) stimulated the sexual behaviour more than any of the other steroids. The combination of OEB (0-33 mg) and DHTB (1 mg) was no more effective than either of these steroids given alone. The function of the accessory sexual glands was stimulated to a level comparable to that of intact animals given TB. Dihydrotestosterone benzoate was, however, not very effective in this respect. Oestradiol benzoate alone or in combination with DHTB caused hypertrophy and very low secretory activity of the seminal vesicles. These results suggest that testosterone itself is active both in the brain and in the accessory sexual glands in rabbits. This is in contrast to the rat, in which aromatization to oestradiol in the brain and reduction to DHT in the periphery seems to be important.

Animals↗

Sexual behaviour of neonatally castrated rats injected during infancy with oestrogen and dihydrotestosterone.

Male rats were castrated on the day of birth (day 1) and injected with either testosterone, dihydrotestosterone, a synthetic oestrogen (RU 2858 + dihydrotestosterone, or oil from days 1 to 5. The aromatizable androgen, testosterone, and RU 2858 suppressed both cyclic gonadotrophin secretion, indicated by the absence of corpora lutea from implanted ovarian grafts, and the behavioural response to oestradiol benzoate + progesterone injections in adulthood. The 5alpha-reduced androgen, dihydrotestosterone alone did not affect gonadotrophin secretion or female receptive behaviour, but like testosterone, it increased penis development in response to testosterone propionate, and this was positively correlated with copulatory efficiency, i.e. the ratio of intromission to mount frequencies. Nevertheless, ejaculation only occurred among animals that had received testosterone or RU 2858 + dihydrotestosterone. The results support the concept that during the preinatal period, neural conversion of androgens to oestrogens is important both for the suppression of female gonadotrophin secretion and behaviour patterns as well as for the organization of male behaviour patterns. The 5alpha-reduction of unsaturated C19-steriods to dihydrotestosterone in peripheral tissues is also required to complete the development of the male genital tract.

Animals↗

Activation of sexual behaviour in castrated rats with the synthetic androgen 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (R 1881).

Castrated sexually inactive rats were treated with the synthetic androgen 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-triene-3-one (methyltrienolone, R 1881), testosterone benzoate (TB), 5 alpha-dihydrotestosterone benzoate (DHTB) or oestradiol benzoate (OB) and tested for sexual behaviour. The synthetic androgen, R 1881, was as potent as TB in stimulating sexual behaviour and OB stimulated all aspects of copulatory behaviour but DHTB had no significant effect. The synthetic androgen, R 1881, is not metabolized by target cells and rapid metabolism could explain the failure of DHTB to stimulate sexual behaviour.

Androgens↗

Actions of catechol oestrogens on concentrations of serum luteinizing hormone in the adult castrated rat: various effects of 4-hydroxyoestradiol and 2-hydroxyoestradiol.

The pharmacological effect of 2-hydroxyoestradiol (2-OHE2) and 4-OHE2 on concentrations of LH in the chronically castrated rat have been compared with that of oestradiol in order to determine whether the in-vivo activity is altered by insertion of a hydroxyl group at position 2 or 4 of the aromatic A ring; these derivatives are naturally occurring oestrogen metabolites. Four groups of six adult male rats were used 4 weeks after bilateral orchidectomy. The right jugular vein was exposed under ether anaesthesia and a basal blood sample taken (10.00 h) immediately before an intravenous injection of vehicle alone (0.1 ml ethanol with 0.01% ascorbic acid), oestradiol, 2-OHE2 or 4-OHE2 (10 micrograms of each in 0.1 ml vehicle). Blood was taken from each animal at 2, 4, 6, 8 and 24 h after treatment and serum assayed for LH. Baseline LH levels were similar in the four groups. At 2 h there was no change in 2-OHE2-treated rats but there was a significant decrease of serum levels of LH in rats treated with oestradiol and 4-OHE2 compared with vehicle-treated controls. The decrease in LH was quantitatively similar in oestradiol- and 4-OHE2-treated groups and was sustained at 4, 6 and 8 h, returning to control values at 24 h. In subsequent experiments the effects of lower doses of these two steroids were compared and the potency of 4-OHE2 was estimated to be about 25% that of oestradiol. In a further experiment, 2-OHE2 (100 micrograms) had no effect when given alone, but when injected i.v. immediately before treatment with 1 microgram oestradiol, it was able to inhibit the suppression of LH by oestradiol. In conclusion, 4-OHE2 had a potent effect in lowering plasma LH levels whereas 2-OHE2, even at a high dose (100 micrograms), did not suppress LH but it was able to inhibit the effect of oestradiol. These differences in biological activity may reflect more rapid metabolism of 2-OHE2 or differences in binding properties of these catechol oestrogens to the oestrogen receptor.

Animals↗

Effect of unilateral castration and unilateral cryptorchidism on gonadotropin and testosterone response to gonadotropin releasing hormone in the bull.

The effects of unilateral castration (UC) and induced unilateral cryptorchidism (UCR) on basal plasma luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone, and on the responses of these hormones to gonadotropin releasing hormone (GnRH), were investigated in bulls altered at 3, 6 or 9 months of age. Blood plasma was collected before and after GnRH (200 micrograms) stimulation approximately 1 year following gonadal manipulation. Neither mean baseline concentrations nor GnRH-induced increases in plasma testosterone were altered (P greater than .1) by hemicastration or UCR (P greater than .1). Both mean baseline LH and GnRH-induced LH release were greater (P less than .05) in bulls altered at 3 months of age than in bulls altered at 9 months of age. UC increased (P less than .05) plasma LH response to GnRH over that observed in intact bulls, but not above that in UCR bulls. UCR had no detectable effect on either baseline concentrations or GnRH-stimulated LH release. FSH was increased (P less than .05) in hemicastrates, while UCR had a variable effect on peripheral FSH: FSH was reduced (P less than .05) in UCR animals altered at 3 months of age but increased (P less than .05) in UCR bulls altered at both 6 and 9 months of age when compared to FSH in intact bulls. The results indicate that, compared with intact bulls, UC bulls release increased amounts of both gonadotropins but similar amounts of testosterone in response to GnRH stimulation. UCR had a variable effect on FSH release and did not alter either LH or testosterone.

Animals↗