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The evolution of the concept of the use of surgical castration in the palliation of breast cancer in pre-menopausal females.

The understanding of the association of mammalian ovarian function with lactation was common knowledge to dairy-men early in the 19th century or earlier. This thesis reviews the application of these empiric observations to lactation in humans by Beatson of Glasgow, supported by his preliminary laboratory investigations. Beatson noted the cellular anatomic similarity between pre-gestational breast and carcinoma. This study reviews the progressive development of the successful clinical application of castration for the control of inoperable breast cancer by Beatson in pre-menopausal women in 1895. The review terminates with its leading to the monumental work of Huggins in 1941.

Breast Neoplasms↗

The effects of castration and testosterone administration on mast cells and hydroxyproline in rat skin.

In rat skin of both sexes, significantly higher concentrations of mast cells were observed in the genital area as compared with the skin of the back. The hydroxyproline (HPL) value in the preputial skin was half that in the dorsal skin. The influence of castration and the administration of testosterone on male rat skin mast cells and HPL were investigated. A possible relationship was pointed out between HPL value and the mast cell population of the skin.

Animals↗

Control of gonadotrophin secretion by steroid hormones in castrated male transsexuals. II. Effects of androgens alone and in combination with oestradiol on the secretions of FSH and LH.

Twenty-nine infusions in twenty castrated male transsexual volunteers were carried out over a period of 7 h with subjects lying in the supine position. The effects of different doses of testosterone and its 5 alpha-reduced metabolites as well as the effect of testosterone in combination with oestradiol on gonadotrophin secretion were evaluated. Different and varying degrees of suppression of plasma levels of FSH and LH were observed. The infusions of 2.4 mg testosterone, 5 alpha-androstan-3 alpha-17 beta-diol (3 alpha-diol), 5 alpha-androstan-3 beta-17 beta-diol (3 beta-diol) but not dihydrotestosterone (DHT) caused significant suppression of LH. FSH, on the other hand was not significantly inhibited by the androgens at this rate. At higher doses all four androgens suppressed LH secretion significantly. FSH was similarly suppressed by the androgens except by DHT. A differential effect on FSH and LH secretions was noted with the combined regime of testosterone and oestradiol. The combined regime did not cause a significantly higher degree of FSH suppression compared with either 200 microgram of oestradiol or 12 mg of testosterone infused alone. The level of LH, however, was suppressed to a greater extent than either of the hormones when given alone. The inhibitory effect of testosterone demonstrated in this study could be due to the parent hormone or its 5 alpha-reduced metabolites. Pharmacological doses of testosterone could exert a greater degree of LH suppression through its conversion to oestradiol. It is likely that oestradiol and testosterone act on gonadotrophin secretion through different mechanisms and that they have an additive suppressive effect on the secretion of LH but not FSH. The potencies for the androgens to suppress gonadotrophin secretion can be ranked as: 3 alpha-diol = 3 beta-diol greater than testosterone greater than dihydrotestosterone.

Androgens↗

Acid hydrolases in the epididymis of normal, castrated, vasectomized, cryptorchid and cryptepididymal rats.

With the aim of gaining knowledge about the lysosomal apparatus of the rat epididymis, four acid hydrolases were analysed in homogenates of the whole organ and, in other experiments, in separated segments: proximal and distal caput, corpus and cauda. The activities were similar to those in the liver, and they were 50% recovered in a cytosol of 43 000 g x 60 min. Ten days after castration all segments showed similar changes, the activities of beta-glucuronidase and cathepsin D increased above normal levels while those of DNAase and acid phosphatase were found slightly decreased. After vasectomy region I (caput and corpus) showed decreased beta-glucuronidase activity and increased acid phosphatase activity. The activity of cathepsin D increased in both regions. In cryptorchid rats (90 days) the epididymis greatly decreased in weight, the activities of acid phosphatase and DNAase slightly decreased in region II (cauda) and in region I, respectively. In the abdominal epididymis (90 days) only region II decreased in weight. DNAase activity decreased in region I while cathepsin D did so in both regions. The results showed that a) the enzymes behave quite independently from each other, suggesting the existence of a specific regulation for each of them b) there were characteristic changes in enzymatic activity for each experimental condition.

Acid Phosphatase↗

An assessment of inhibin-like activity secreted by Sertoli cells in culture using castrated adult male rats.

Sertoli cells isolated from testes of 16-18 days old male rats were maintained in culture. Incubation media from these culture were pooled on day 7 and tested for its inhibin-like activity either with (SCCM) or after charcoal treatment (CSCCM) in castrated adult male rats. The assay was based on the tacit assumption that SCCM or CSCCM would specifically lower circulating blood serum levels of FSH. Subcutaneous (sc)injections of CSCCM at a dose level of 1 mg protein per rat, per day, x 3 days caused a specific suppression of FSH levels, while lower dosages of CSCCM (Protein content of 300 micrograms or 600 micrograms/rat/day, x 3 days) were without any affect on basal levels of FSH and LH. SCCM was ineffective at all dose levels tested. Intracardiac injections of varying doses of LHRH (25 to 400 ng/rat) to CSCCM pre-treated rats (200 micrograms/rat/day, x 3 days) failed to increase the levels of LH and FSH. These results support the presence of inhibin like activity in SCCM by a bioassay procedure alternate to in vitro pituitary cell culture system used by other investigators.

Animals↗

Control of gonadotrophin secretion by steroid hormones in male castrates: site of oestradiol action.

Four normal healthy castrated male transsexuals who were not on hormone therapy for at least 4 months volunteered for this study. Each subject received 3 infusions at weekly intervals--the first consisting of LHRH alone, the second of LHRH and oestradiol and the third of oestradiol alone. Venous blood samples were collected at 20-minute intervals 1 hour before the start and during the whole period of infusion. Plasma concentrations of FSH, LH and oestradiol were measured by radio-immunoassay. On an average, 100 micrograms of LHRH enhanced the area under the LH secretion curve by 177% and under the FSH curve by 68%. Oestradiol had a differential effect on the endogenous secretion of LH and FSH, suppressing them by 53% and 18%, respectively. Similarly, the LHRH-stimulated release of LH was significantly inhibited to a greater extent (42%) than that of FSH (23%, P less than 0.05; paired t test). Such an observation and in the light of our acceptance of the single releasing hormone theory, suggests that the differential actions of oestradiol on the secretions of FSH and LH are due to mechanisms residing in the pituitary.

Castration↗

Castration complex. Evidence from men operated for hypospadias.

Thirty-three adult hypospadiacs and 36 matched controls were investigated by means of Rorschach's test, in a double-blind design. From psychoanalytic theory predictions were made about the effects of the influences of the genital malformation and its treatment on the psychological adjustment. The hypospadiacs differed significantly from the controls as predicted. They exhibited more neurotic constriction with less ego-strength and less utilization of resources. Their anxiety and hostility levels were judged higher and they showed less self-esteem and activity as well as less capacity for interpersonal relations. The results are compatible with psychoanalytic theory on the role of castration anxiety in the neurosis formation. The need for psychotherapeutic support for these boys and their parents is stressed.

Adult↗

The prostatic lobes and the seminal vesicles in non-diabetic and alloxan-diabetic castrated adrenalectomized rats injected with cortisone.

The growth of the prostatic lobes and the seminal vesicles was studied morphologically in alloxan-diabetic and non-diabetic castrated adrenalectomized rats. In non-diabetic but not in alloxan-diabetic rats cortisone in daily doses of 3 or 6 mg induced growth and secretory activity in the epithelium of the dorsolateral prostate, the coagulating glands and the seminal vesicles. Insulin administration to alloxan-diabetic rats could restore the effect of cortisone on these glands. This indicates that insulin deficiency per se was the main reason for the failure of cortisone to induce secretory activity of the prostatic lobes and the seminal vesicles of alloxan-diabetic rats.

Adrenalectomy↗

The effect of lighting conditions on plasma levels of gonadotropins in castrated male rats.

Plasma levels of LH and FSH were measured in castrated male rats kept in a 12/12 h light/dark cycle (control lighting), continuous light or continuous darkness. In Experiment I, the animals were kept in the three illumination conditions for 5 weeks. They were then decapitated for blood collection. In Experiment II, the blood samples were collected daily via permanently implanted aortic cannulae after 7 days of adaptation to the experimental lighting condition. In both experiments, the plasma levels of LH and FSH were higher in the rats kept in continuous light than in those kept in control conditions. After exposure to darkness for 5 weeks, the gonadotropin levels did not differ from the control values. In Experiment II, the levels of FSH were lower in darkness than in the control lighting, but the levels of LH did not change.

Animals↗

A clinical trial of three anaesthetic regimens for the castration of ponies.

After premedication with intravenous xylazine 30 ponies were anaesthetised for castration under field conditions with intravenous ketamine, thiopentone or methohexitone. The duration of anaesthesia was adequate for surgery and the times taken to stand were similar in each group. The recovery of the ponies after ketamine was quieter than after either of the barbiturates and this may be an advantage when skilled assistance is lacking. However, all the anaesthetics appeared to be suitable for performing minor surgery in the field.

Anesthesia, General↗

Comparison of the Burdizzo and rubber ring methods for castrating and tail docking lambs.

The behavioural and plasma cortisol changes in groups of six lambs, five to six days old, were used to compare the acute effects of four methods of castration and tail docking: Burdizzo, standard sized and small rubber rings, and a combined method in which the application of a standard rubber ring was followed immediately by the application of the Burdizzo just distal to it. A control group was also included. Active behaviours such as foot stamping and restlessness increased markedly only after the treatments with rubber rings. Less time was spent in abnormal postures, and the increases in plasma cortisol were least after the combined method. It was concluded that the lambs treated by all the methods suffered considerable acute pain, for up to three hours in some cases, but that the combined method produced the least pain as judged by the behavioural and physiological indices measured, and that the small rubber rings produced more intense pain for a shorter time than the standard rubber rings.

Acute Disease↗

Activation of feminine sexual behavior in castrated male rats by intrahypothalamic implants of estradiol benzoate.

The effects of intracerebral estradiol benzoate (EB) implants upon lordosis behavior in castrated male rats were investigated. 27 guage EB-filled or Blank implants were placed unilaterally in either the preoptic area (POA) or the region of the ventromedial hypothalamic nucleus (VMH). When 0.5 microgram of EB was administered subcutaneously for eight days, males with EB implants had significantly higher lordosis quotients (LQ) than males with Blank implants. EB implants located in the region of the VMH were significantly more effective in stimulating lordosis responses than implants in the POA. These results indicate that, in male rats as in females, the VMH region is a primary site for the hormonal activation of lordosis behavior.

Animals↗

Effect of melatonin and superior cervical ganglioectomy on luteinizing hormone on release induced by estradiol-progesterone in castrated rats.

The effect of melatonin on luteinizing hormone (LH) relase was studied in castrated female rats injected with estradiol and progesterone. Melatonin administered s.c. twice daily for 6 days exerted a biphasic, dose-related effect on LH release, the lowest dose (125 micrograms/100 g body weight) being stimulatory and the highest (250 micrograms/100 g body weight) inhibitory. Superior cervical ganglionectomy negated the inhibitory effect of the high metatonin dose on steroid-induced LH release. Rather melatonin injection to ganglionectomized rats resulted in significantly higher serum LH values than those of animals injected with estradiol and progesterone alone. Melatonin treatment failed to modify postcastration serum LH levels.

Animals↗

Catecholestrogens affect catecholamine turnover rates in the anterior part of the mediobasal hypothalamus and medial preoptic area in the male and female castrated rat.

To study the interactions of catecholestrogens with the catecholamine system we estimated the catecholamine concentrations and turnover rates in the anterior part of the mediobasal hypothalamus (AMBH) and medial preoptic area (MPO) following 2-hydroxyestradiol-17 beta (2-OHE2) or 2-hydroxyestrone (2-HOE1) treatment in castrated male and female rats. Serum concentrations of LH and prolactin were also measured. The turnover rates of catecholamines were calculated by monitoring the catecholamine loss 1 h after blocking the catecholamine synthesis with alpha-methyl-p-tyrosine. Dopamine, epinephrine and norepinephrine concentrations were measured by a radioenzymatic assay. In males, 2-OHE2 (50 micrograms/kg) and 2-OHE1 (50 micrograms/kg) resulted in decreased serum LH values (p less than 0.05) 4 and 5 h after treatment. None of these 2-hydroxylated estrogens were able to alter serum prolactin levels significantly. There was a decline in epinephrine and norepinephrine concentrations in the AMBH. The greatest change in catecholamine turnover rates in response to catecholestrogen treatment also occurred in the AMBH. 2-OHE2 and 2-OHE1 reduced turnover rates of dopamine, norepinephrine and epinephrine in the AMBH. Only the dopamine turnover rate was affected in the MPO, where it increased following 2-OHE2 treatment. In females, only 2-OHE2 (50 micrograms/kg) was effective in decreasing serum LH (p less than 0.05) and increasing prolactin (p less than 0.01) levels. Dopamine and epinephrine concentrations as well as their turnover rates declined in the AMBH after treatment with catecholestrogens. The concentration and turnover rate of epinephrine also decreased in the MPO. There was no significant change in norepinephrine concentration or turnover rate. It is suggested that 2-hydroxyestrogens are possibly involved in mechanisms which are inhibitory to LH secretion and stimulatory to prolactin release. These actions appear to be partly mediated by catecholamines.

Animals↗

Testosterone raises LHRH levels exclusively in the median eminence of castrated rats.

Although LHRH is widely distributed in the diencephalon, previous studies show that testosterone (T) treatment for 72-96 h of castrated male rats raised LHRH levels only in the medial basal hypothalamus. In the present study, LHRH concentrations were analyzed in microdissected brain regions shown to contain LHRH perikarya and their projections to identify the discrete regions which may display this T-dependent accumulation of luteinizing hormone-releasing hormone (LHRH) and to study the temporal sequence of LHRH changes in those regions. Rats were killed at 12-hour intervals from 60 to 96 h after subcutaneous implantation of Silastic capsules containing T. Results showed that the physiological range of serum T levels attained by these implants suppressed LH release at all times, however, there was no immediate effect on LHRH concentrations in any region. In fact, out of the 9 regions in the preoptic-tuberal pathway examined, 8 regions displayed no change in LHRH concentrations at any time. On the other hand, for up to 84 h, LHRH concentrations in the median eminence region remained unchanged; an additional 12 h of T exposure significantly raised LHRH levels. These results suggest that this T-dependent accumulation of LHRH may arise either by de novo synthesis or by increase in the rate of processing of the precursor LHRH protein into the immunoreactive form within nerve terminals in the median eminence.

Animals↗

Insulin-induced hypoglycemia decreases luteinizing hormone secretion in the castrated male rat: involvement of opiate peptides.

Insulin-induced hypoglycemia (IIH) has been reported to inhibit luteinizing hormone (LH) secretion in ovariectomized ewes as well as in intact or gonadectomized female rhesus monkeys. An infusion of naloxone, a specific opiate receptor antagonist, while able to prevent this inhibitory effect in ewes, was ineffective in monkeys, suggesting a difference in the mechanisms involved in the response to IIH in these two species. The present study was designed to investigate the influence of this stimulus on the dynamics of LH release and the possible activation of an opioidergic pathway in the long-term castrated male rat. Blood samples were collected every 7 min, for several hours, in freely-moving rats bearing a jugular cannula. The intravenous injection of 0.4 IU of insulin triggered an acute hypoglycemia and reduced LH release. In contrast, during a continuous intravenous naloxone infusion (0.5 mg/kg/h), insulin, while still lowering the glycemia, failed to affect the LH secretory pattern. In a control experiment, naloxone infusion alone had no significant effect on mean LH concentration and pulse intervals. These experiments indicate that, in long-term gonadectomized male rats, IIH impairs the LH secretory pattern, and that endogenous opioid peptides are involved in this response.

Animals↗

Surface features of epithelium of the seminal vesicle in young adult and old guinea pigs and after castration.

The study involves an SEM examination of the guinea pig seminal vesicle in both normal and old animals and after orchiectomy. The mucosa showed complicated anastomosing folds. The surface cells were characterized by dense and long microvilli. The density of microvilli decreased in old animals. The lateral surfaces were relatively smooth with few ridges interlocking with the neighbouring cells. The irregular basal surface was covered by basal lamina richly endowed with fine collagenous fibres derived from the loose subepithelial stroma. After orchiectomy the mucosal folds were less prominent. The cells were shorter and with sparse and short microvilli while the subepithelial stroma became more condense. Rejection or degeneration of glandular cells were observed. This shows that the morphology of the luminal surfaces is related to age and stages of function and that castration results in a reduction of microvilli and causes degeneration of cells.

Aging↗