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Effects of LH-RH infusion, castration and cryptorchidism on gonadotrophin and testosterone secretion in developing rams.

The relationship between the pituitary gland and testis in rams was studied from birth to sexual maturity. The concentrations of LH, FSH and testosterone increased between 5 and 7 weeks of age; the rise was not correlated with any specific cytological change in the testis. An augmented pituitary response to LH-RH was demonstrated as levels of gonadotrophin increased. It is unclear whether this change in sensitivity plays a role in initiation of the pubertal process because Sertoli cell maturation, the earliest detectable change in the seminiferous epithelium, occurs between 17 and 21 weeks of age. Spermatocytes were first seen in biopsies taken at 31-36 weeks and spermatogenesis was established fully by 45 weeks. This second phase of testicular development was characterized by increases in prolactin, testosterone and LH. Leydig cells previously difficult to identify became recognizable at the time of sexual maturation. In newborn rams, castration produced significant increases in LH and FSH levels within 2-3 weeks, but higher basal FSH levels (2- to 3-fold) were observed at 5 than at 3 weeks of age. Cryptorchidism did not elevate LH or FSH significantly during the first year of life. FSH rose after this period to levels 2- to 3-fold higher than in normal rams, while LH and testosterone values remained in the normal range in spite of diminished spermatogenic activity; spermatids were absent and testis size was approximately 60% of that recorded in a normal ram. These studies demonstrate a rise in gonadotrophin and testosterone secretion in rams during the first 5-7 weeks of life, followed by a quiescent period of 8-9 months before a secondary increase occurs coincident with the establishment of sexual maturity.

Aging↗

[Various characteristics of the synthesis of nucleic acids and proteins in the prostate of castrated rabbits after separate and successive administration of testosterone and 5 alpha-dihydrotestosterone].

The results are presented of studying nucleic acid and protein synthesis in the rabbit prostate. It was shown that incorporation of radioactive precursors into the prostate DNA, RNA and proteins is diminished two months after gonadectomy of the animals. Testosterone and its metabolite 5 alpha-dihydrotestosterone markedly intensify RNA and protein synthesis in the prostate of castrated rabbits, whereas 5 alpha-dihydrotestosterone only exerts a stimulating effect upon DNA synthesis. Preliminary testosterone propionate injections to gonadectomized rabbits delay DNA synthesis, induced by 5 alpha-dihydrotestosterone, and decrease the marker incorporation into RNA and protein, comparatively to the effect of each separate androgen.

Animals↗

Effect of melatonin-free pineal extract on prolactin in castrated and thyrotropin releasing hormone-stimulated rats.

Administration of a melatonin-free pineal extract to the rat induced the following effects on prolactin: a) under basal conditions, after 4 hrs from a single injection or after 3 days of treatment, there was a decrease of 34% and 28% respectively, in serum prolactin, with no change in the pituitary content of this hormone; b) when prolactin was stimulated by castration the decrease of the serum level of this hormone (-37%) was accompanied by a decrease in its pituitary content (-33%) and concentration (-35%); c) under conditions of exogenous TRH stimulation the decrease in serum prolactin (-26%) was accompanied by a decrease in pituitary prolactin content (-27%) and concentration (-21%), the latter two without statistical significance. The role of the pineal gland on prolactin is discussed.

Animals↗

[The effect of testosterone propionate, 5 alpha-dihydrotestosterone and 5 alpha-androstan-3 beta, 17 beta-diol on acid phosphatase activity in the prostate of castrated rats].

The acid phosphatase is studied in the prostate gland of rats. It is shown that 10 days after gonadectomy the activity of acid phosphatase lowered considerably. Administration of testosterone propionate or 5 alpha-dihydrotestosterone to castrated animals restored the enzyme activity whereas 5 alpha-androstan-3 beta,17-diol was not effective. Administration of testosterone propionate with one of its metabolites increased the activity of acid phosphatase in the prostate gland, however to a less extent than with the use of the hormone itself. The lowest activity is detected with the simultaneous application of three androgens.

Acid Phosphatase↗

Relations between 3H-estradiol uptake and receptor content of estrogen responsive tissues of castrated female rat.

The time course of 3H-Estradiol-17 beta (3H-E2) uptake, and estrogen receptor content in estrogen responsive tissues were studied between 0 and 12 h after injection of 0.5 microgram/kg of 3H-E2 or cold E2 injection to castrated adult female rats. The plasma concentration of 3H-E2 between 10 min and 2 h after injection was in the range of the plasma E2 level of cyclic rat. The total 3H-E2 uptake was well correlated with the receptor content in all tissues. The rank order of 3H-E2 uptake was: uterus (Ut) greater than anterior pituitary (Ap) greater than hypothalamus (Ht) greater than plasma. The cytosol 3H-E2 uptake showed its maximal level 10 min after injection in all tissues. Parallel time course between plasma 3H-E2 and cytosol uptake was obtained for each separate tissue. The nuclear 3H-E2 uptake showed its maximal values 2 h after injection with a subsequent decline. Cytosolic estrogen receptor (Rc) content showed a depletion-replenishment cycle after cold E2 injection in all tissues. Nuclear estrogen receptor (Rn) content in Ut increased progressively from 0 to 14 h after injection, but in Ap it showed its maximal level 2 h after injection, declining afterwards. In Ap, nuclear 3H-E2 uptake and Rn level showed parallel time courses. The maximal level of both parameters coinciding with the time of maximal Rc depletion. However, the Rn level in Ut increases more slowly at greater length than the nuclear 3H-E2 uptake, both processes being divergent. These findings are interpreted as the expression of tissular differences in the rate of nuclear receptor formation from the Rc-E complex previously translocated into nucleus and attached to chromatin.

Animals↗

[Reaction of the ovary of the young rat to transplantation into the spleen of adult castrated diabetic animals].

The ovary of an infantile rat was grafted into the spleen of adult castrated females. After 7-9 days half of the animals were injected with alloxan subcutaneously. The rats were decapitated 33 days after ovary grafting. In all diabetic rats and 62% of the control animals, the vaginal smears showed persistent diestrus. The height of the uterine epithelium was fairly low. Persistent estrus was detected in 38% of the control animals. In the diabetic group, the degree of ovarian hypertrophy was significantly lower than in the control group, although no differences were discovered in pituitary gonadotropin content in both the groups. It is suggested that the pituitary of diabetic animals slightly responds to estrogenic deficiency. This was manifested in a lesser degree of ovarian hypertrophy and in the absence in the ovaries of the majority of diabetic rats of the phenomena such as the proliferation of the connective tissue and the appearance of granulocellular tissue accumulations.

Aging↗

Effects of castration and replacement of androgen on the separation of rat ventral prostate cells by Ficoll gradient centrifugation.

When regressing or growing (hypertrophic) cells from collagenase-digested ventral prostates were centrifuged on isokinetic Ficoll gradients for 6-8 min, they distributed into four fractions. Because of changes in epithelial cell morphology and density following castration to induce regression and replacement of androgens to cause cell growth, and contrary to results with normal rat ventral prostate, stromal cell fraction 2 was contaminated to a greater extent with regressing epithelial cells, as judged by their morphology and binding of radioactive androgens. However, centrifugation for 3 min increased the purity of epithelial cell fraction 4, although the yield of desired cells was reduced. Most cells from endocrine-manipulated rats were viable, as judged by exclusion of trypan blue and the initial incorporation of 3H-uridine. Cells centrifuged on a similar gradient of Percoll separated by a 'sieving' effect, which inverted the order of cellular fractions and removed red blood cells from fraction 2. Metrizamide offered no advantages, compared with Ficoll or Percoll. Neither physiologic nor pharmacologic amounts of testosterone returned the morphology of isolated epithelial cells to normal. To obtain consistent results with prostates from normal or hormone-manipulated rats, one should take care to select an active preparation of collagenase, avoid the use of very old animals, cool the tissue after it is dissociated, and do not apply undigested clumps of cells or overload the gradient. If attention is paid to these details, populations enriched in viable regressing or growing prostate epithelial or stromal cells can be obtained from hormonally manipulated rats.

Androgens↗

[Effect of castration on purine biosynthesis in the rat liver and kidney].

With the present study, the effects of testosterone deficiency on the biosynthesis of purine nucleotides and nucleic acids in rat liver and kidney has been investigated. 20% homogenates were prepared in 1 N HCl04, centrifuged and the nucleic acid were extracted from the precipitate with 0.7 N PCA (15 min at 90 degrees C): the acid-soluble purines were precipitated with 1 M AgNO3 from the supernatant of the centrifuged homogenate, then extracted with 1 M HC1. An increase of the specific activity of the liver (A, +49%; G, +47%) and of the kidney (A, +54%; G, +34%) has been observed (P less than 0.05), while no variation of the specific activity of nucleic acids was evident after castration.

Adenine↗

Effect of immunological castration on sexual and production characteristics in male cattle.

Ten male Friesian calves were actively immunised against luteinising hormone releasing hormone and their production compared with 10 Friesian steer calves. Five of the immunised calves responded poorly (group 1); the other five responded well (group 2), resulting in high antibody titres, low serum testosterone levels, involuted testes, reduced libido and semen production, and docile behavior. The castration effect lasted approximately six months before reversion to near normal male status. This temporary immunocastration failed to affect seriously performance until slaughter, and liveweight gain was substantially better in this group than in the steers. Carcase traits were similar in groups 1 and 2, but the lean content in both was considerably greater than in the steer carcases.

Animals↗

[Plasma LH-RH levels in normal men and women with increasing age, in women with castration, climacteric syndrome, also in pregnancy, delivery and puerperium].

In order to further clarify hypothalamic function, plasma LH-RH was measured by a sensitive radioimmunoassay in normal men and women with increasing age, in women with castration, climacteric syndrome, also in pregnancy, deliver, and puerperium. The following results were obtained: 1) Plasma LH-RH levels were the same in the follicular and luteal phases of adult and premenopausal women, and a gradual increase was noted through the premenopausal period. It had the highest peak in the group within one year after menopause, followed thereafter by a gradual decline throughout the senile period but still remaining higher than that in the adult period. 2) There was no change in plasma LH-RH in men between ages 22 and 55, but a slight increase was found over age 56. 3) There was a high plasma LH-RH peak in the first day after bilateral oophorectomy both in pre- and post-menopausal women. A slight increase was found postoperatively in the premenopausal but not in the postmenopausal group. 4) There was a low plasma LH-RH level in both pre- and post-menopausal women with climacteric syndromes. 5) There was a low plasma LH-RH level through 9-39 weeks of gestation and during labor, it became a little higher at one month postpartum than in non-pregnant women.

Adult↗

Pituitary and hypothalamic action of progestagens in castrated female rats.

Different doses of progesterone, D-norgestrel and delta 15-D-norgestrel were injected subcutaneously for 7 days to female rats castrated 7 days prior to the experiments. One day after the last steroid injection a i.p. LH-RH test was performed, blood samples were collected by heart puncture and serum levels of r-LH and r-FSH were estimated by radioimmunoassay. LH-RH serum levels were determined in progestagen treated control groups by an anterior pituitary cell culture bioassay. Dose dependent inhibitory effects of steroids on LH-RH stimulated gonadotropin release were observed and a dissociation of r-LH and r-FSH serum levels was found. The modulatory influence of progestagens used in this study on LH-RH provoked gonadotropin release correlated with their biological efficiency evaluated in the Clauberg test. Progesterone, D-norgestrel and delta 15-D-norgestrel treatment had no significant effects on basal r-LH levels, but LH-RH provoked r-LH levels were higher than in the control animals. Progesterone and D-norgestrel suppressed basal as LH-RH stimulated r-FSH levels, whereas delta 15-D-norgestrel showed a complex influence on r-FSH secretion. A progestagen stimulated rise of LH-RH serum levels was found and indicated an additional effect of these hormones at the hypothalamic level. These data suggest the action of progestagens at various levels of the hypothalamus-pituitary axis.

Animals↗

Bipotentiality of response to sex hormones by the prostate of castrated or hypophysectomized dogs. Direct effects of estrogen.

Prostatic response to administered estradiol-17beta 17-cyclopentylpropionate (ECP) was studied in castrated or hypophysectomized dogs. Ultrastructural investigation identified two types of epithelial cells, squamous and modified glandular, that resulted from estrogen action. Squamous cells, which predominated, appeared to evolve from basal reserve cells. Estrogen-modified glandular cells have features attributable to estrogen and previous androgen stimulation. Thaw-mount autoradiography of explants located radiolabeled estrogen in prostatic epithelium and stroma of normal and ECP-treated animals, suggesting a role of estrogen in prostatic homeostasis. Epithelium from ECP-treated dogs incorporated 3H-thymidine, indicating that estrogen promotes DNA synthesis in these cells. Greatly enhanced conversion of radiotestosterone to 4-androstene-3,17-dione, with sharply decreased formation of 5alpha-reduced hydroxylation products, and attendant elevation in estradiol-17beta oxidoreductase activity are metabolic markers attributable to the induced squamous and responding stromal cells. The duality of prostatic response to sex hormones is apparent from observations that estrogen stimulates regressed glandular epithelium which had undergone androgen-mediated differentiation before ablation.

Animals↗

Effect of castration on male-determined acceleration of autoimmune disease in BXSB mice.

The autoimmune disease of BXSB mice is markedly accelerated by a Y chromosome-associated male-specific factor. In order to investigate the mechanism of this effect, we castrated male and female BXSB mice at 10 days of age and compared the course of development of their autoimmune syndrome with that of sham-operated, sex-matched, littermate controls. Orchiectomy did not delay the early onset of fatal immunopathology in males, and oophorectomy did not exacerbate the indolent progression of morbidity in females. We conclude, therefore, that the male-specific effect that accelerates BXSB autoimmune disease is not hormonally mediated.

Animals↗

[Changes in the concentration of luteinizing hormone in the blood serum and of luliberin in the hypothalamus of castrated rats after the administration of testosterone and its 5 alpha-reduced metabolites. I].

Luteinizing hormone concentration in the blood serum and luliberin content in the hypothalamic arcuate body and medial eminence were determined in castrated mature rats 1, 3, 6, 12, 24 hours afte single injections of testosterone and its 5 alpha-reduced metabolites (dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol) at a dose of 2.5 x 10(-7) kg/kg body weight by radioimmunoassay. Principal differences between testosterone and its 5 alpha-reduced metabolite action on the hypothalamohypophyseal system were detected from the stand point of their effectiveness and the effect realization rate.

Animals↗

[Effect of castration and testosterone propionate on 3H-noradrenaline metabolism in different brain structures in male rats].

Experimental results demonstrated that castration in male rats led to the changes in catecholamine metabolism in various regions of the brian. In particular there is an acceleration of labeled noradrenalin- disappearance (3H-noradrenaline) from the limbic system of the hypothalamus formations. Testosterone propionate restored the initial level of 3H-noradrenaline in the mentioned structures of the brain. The data obtained indicated that adrenorecption of the rynecephalo-hypothalamic complex took part in the central regulation of the gonadotropic function of the hypophysis.

Animals↗

Initiation of copulatory behaviour in castrated male rats implanted with very small testosterone-filled silastic capsules.

Adult, sexually experienced male rats were castrated and two weeks later implanted with 5 or 10 mm long testosterone-filled silastic capsules (inner diameter 1.4 mm). From the seventh up to the fourteenth week following implantation the majority of males was found to be in the state at which they initiated copulatory behaviour with proceptive (darting) females but not with passively receptive (lordotic) females. Being in this state, their copulatory performance was comparable with precastration level except the decreased frequency of intromission befor the first ejaculation. As to the precopulatory behaviour, the males displayed it even towards females which did not stimulate copulatory behaviour in these males. In all the applied measures no difference between the 5 and 10 mm capsules was revealed. The used implants were found behaviourally effective about fourteen or nineteen weeks throughout following implantation or reimplantation, respectively.

Animals↗

[Changes in the amount of protein in hypothalamic neurons of sexually mature rats castrated neonatally].

A change in the amount of protein in the neurons of the anterior and mediobasal hypothalamus of sexually mature male rats castrated neonatally was observed in the study using the interferometric method. A considerable increase was recorded in the dry weight of the neurons in the medial preoptic region and the arcuate and ventromedial nuclei of the hypothalamus. The most pronounced changes were observed in the nuclei of these neurons. The results obtained point to the influence of androgens on the hypothalamic structures responsible for the regulation of both cyclic and tonic release of gonadotropic hormones in sexually mature animals during sex differentiation of the brain.

Animals↗

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