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V D Castracane

Publications and source records attributed to V D Castracane.

At least 73 records · Page 4Linked to original sources
PubMed1985

Hyperprolactinemia inhibits development of Leydig cell tumors in aging Fischer rats.

In inbred CDF (Fischer 344) male rats autopsied at the age of 18-24 months, testicular tumors were present in 24 of 36 control animals but in none of 28 males rendered hyperprolactinemic by transplantation of anterior pituitaries from adult females under the renal capsules. In another experiment, microscopically detectable Leydig cell adenomas were present in each of 11 control animals at the age of 14.5 months but in none of 11 males in which hyperprolactinemia was induced by treatment with diethylstilbestrol. Development of testicular tumors had initially little effect on basal and hCG-stimulated plasma testosterone and androstenedione levels but eventually led to atrophy of the seminal vesicles. Incubated tumor tissue produced large quantities of progesterone and responded to hCG in vitro by an increase in progesterone but not testosterone secretion. Daily sperm production and epididymal sperm reserves were significantly reduced already during early stages of Leydig cell tumor development. We propose that hyperprolactin prevents development of Leydig cell tumors by suppression of plasma LH levels and suggest that age-related reductions in gametogenic and steroidogenic functions of the testes in Fischer rats are due to development of Leydig cell tumors rather than to aging per se.

Age Factors↗
PubMed1985

Serum androstenedione and testosterone concentrations during pregnancy and nonpregnant cycles in dogs.

Concentrations of testosterone and of androstenedione were determined by radioimmunoassay in serum samples collected every 2-5 days throughout the periovulatory and luteal phases of the ovarian cycles of pregnant and nonpregnant beagle bitches. Testosterone levels were consistently lower than those of androstenedione, reached peaks of 29 +/- 4 ng/dl near the time of the preovulatory luteinizing hormone peak, and were reduced to near the limits of detection (less than or equal to 5-10 ng/dl) throughout the luteal phase. Androstenedione levels reached preovulatory peaks of 73 +/- 13 ng/dl, were 54 +/- 7 ng/ml during early estrus, increased (P less than 0.05) to early luteal phase peaks of 76 +/- 8 ng/dl between Days 6 and 18, and then declined to 41 +/- 5 ng/dl by Day 35-40 in both pregnant (n = 8) and nonpregnant (n = 4) bitches. Subsequent protracted increases in androstenedione occurred in 4 of 8 pregnancies but in none of the nonpregnant bitches. From Days 42 to 64 the differences in mean levels between pregnant (45 +/- 2 ng/ml) and nonpregnant (32 +/- 3 ng/ml) bitches was not significant (P greater than 0.05). At parturition androstenedione levels fell (P less than 0.05) abruptly from 39 +/- 7 to 13 +/- 3 ng/dl. These results suggest that, in the bitch, androstenedione is the major circulating androgen during the follicular and luteal phases and that patterns of androstenedione levels during the luteal phase parallel those reported for progesterone in pregnant and nonpregnant bitches, including maintenance of elevated levels throughout gestation and an abrupt decline at parturition.

Androstenedione↗
PubMed1985

Relaxin in the pregnant baboon: evidence for local production in reproductive tissues.

We examined the nonluteal production of relaxin in the pregnant baboon. In experimental animals (n = 5), the corpus luteum-bearing ovary was removed in early pregnancy (days 25-30), and intact pregnant baboons served as controls. In both groups of baboons, peripheral, uterine, and ovarian venous blood samples and amniotic fluid were collected immediately before hysterotomy, which was performed late in pregnancy (days 139-142). After hysterotomy, samples of reproductive and control tissues were obtained (placenta, decidua, myometrium, fetal membranes, and omentum). Relaxin concentrations were determined in all samples using an antiporcine relaxin RIA. In unilaterally oophorectomized pregnant baboons, peripheral plasma levels of relaxin were below the limits of detection (less than 157 pg/ml) for 100 days following corpus luteum removal, while levels in control pregnant baboons were greater than 1000 pg/ml. Relaxin levels in uterine venous plasma were comparable to peripheral plasma levels in each group. Relaxin concentrations in amniotic fluid of both groups were below the limits of detection (less than 157 pg/ml). Relaxin was found in decidua, placenta, and myometrium in those pregnant baboons in which the corpus luteum-bearing ovary had been removed over 100 days earlier. This finding together with the absence of a relaxin gradient in uterine venous plasma and undetectable relaxin levels in amniotic fluid is a strong indication of local relaxin production in reproductive tissues without contribution to peripheral plasma levels.

Amniotic Fluid↗
PubMed1984

Relationship of conceptus number to the action of luteinizing hormone-antiserum in the pregnant rat.

Treatment of pregnant rats on Day 12 of pregnancy with luteinizing hormone-antiserum (LH-AS) (equine anti-bovine LH) had no effect on the maintenance of pregnancy or serum progesterone levels in rats bearing either 2 or more than 8 conceptuses. In rats with only 1 conceptus, LH-AS administration resulted in a significant decline in serum progesterone to basal levels within 24 h and all animals (n = 6) failed to maintain pregnancy. All rats with either 1, 2 or greater than 8 implantations showed no effect of normal horse serum (NHS) administration. There was no effect of LH-AS administration on serum testosterone levels, compared to NHS-treated controls.

Animals↗
PubMed1984

Nivazol: a glucocorticoid in rats with only hypothalamic-pituitary-adrenal-inhibiting activity in primates.

The synthetic steroid nivazol lacks three of the substituents considered to be important for glucocorticoid activity, i.e. the 3-keto, the 11-hydroxy, and the 20-keto groups. Nevertheless, in the rat, nivazol has the activity profile of a glucocorticoid. After treatment of intact female rats with nivazol , the mean weights of the adrenals and thymus were lower than those in the vehicle-treated control group. The results were qualitatively and quantitatively similar to those obtained with methylprednisolone. Thymolysis as well as liver glycogen deposition were seen in adrenalectomized rats treated with nivazol , and eosinopenia and inhibition of carrageenan edema were noted in intact rats. In the rhesus monkey, treatment with nivazol resulted in a marked reduction in circulating cortisol levels and elimination of the diurnal pattern, although a dose 10 times that needed to reduce circulating cortisol levels did not produce eosinopenia or increase fasting blood glucose levels. Both eosinopenia and higher fasting blood glucose levels were seen after treatment with methylprednisolone. Nivazol did not prevent the ACTH-induced increase in circulating cortisol levels nor did it alter circulating aldosterone levels. Therefore, suppression of ACTH is the predominant if not the sole action of nivazol in the primate. Preliminary results in clinical trials suggest a similar activity profile in humans. Therefore, nivazol elicits numerous glucocorticoid activities in the rodent, but only the inhibition of the hypothalamic-pituitary-adrenal axis was observed in the primate. It is of special interest that the inhibition of the hypothalamic-pituitary-adrenal axis occurs without altering circulating aldosterone levels and without evidence of debilitating catabolic activity.

Aldosterone↗
PubMed1984

Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons.

To evaluate the effects of physiological concentrations of estrogen on plasma concentrations of somatomedin-C (Sm-C) and GH, 16 chronic castrate female baboons were implanted either with blank Silastic capsules (n = 5) or capsules containing crystalline estradiol (E2; n = 11), which remained in place for 7 days. By day 7, serum E2 levels in treated animals rose into the physiological adult female range (mean +/- SEM, 96 +/- 9.2 pg/ml) and were greater (P less than 0.0005) than those in control animals (27.5 +/- 3.4 pg/ml). Sm-C concentrations rose significantly by day 7 in treated animals compared to those in control animals, whether assayed from unprocessed plasma (96% increase; P less than 0.01), plasma pretreated with glycine-HCl (99% increase; P less than 0.01), or plasma extracted with acid-ethanol (72% increase; P less than 0.02). GH concentrations in these animals were low and were not significantly different in E2-treated and control animals. To evaluate the effects of pharmacological doses of E2 on Sm-C and GH concentrations, six intact adult female baboons were treated with six daily injections of 1 mg E2 benzoate in oil. Serum E2 rose to a mean level of 1669 +/- 320 pg/ml on day 7. The plasma Sm-C concentration by day 7 was significantly higher than the pretreatment value whether assayed in untreated plasma (4.3-fold increase; P less than 0.01), plasma pretreated with glycine-HCl (2-fold increase; P less than 0.01), or plasma extracted with acid-ethanol (1.7-fold increase; P less than 0.01). Mean serum GH concentrations rose significantly from 3.3 ng/ml on day 0 to 23.6 ng/ml by day 7 (P less than 0.02). Evaluation of the chromatographic profile of native baboon plasma suggested a marked increase in [125I]Sm-C binding to plasma proteins after in vivo pharmacological E2 treatment; a broad peak of [125I]Sm-C binding over a size range from that of albumin to gamma-globulin was found. These results indicate that estrogen treatment of castrate or intact female baboons with both physiological and pharmacological doses results in an increase in plasma Sm-C concentrations that, at least in pharmacological doses, are mediated through an increase in GH concentrations. Although pharmacological E2 treatment results in a stimulation of plasma proteins that bind Sm-C, the effects on plasma Sm-C concentrations were found after procedures that diminish interference from circulating binding proteins. These data support the concept that estrogen may play a role in the physiological increase in plasma concentrations of Sm-C associated with normal puberty.

Animals↗
PubMed1984

Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats.

The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25-26 days of age, and an Alzet osmotic minipump containing ACTH (1-24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 micrograms of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 +/- 94 vs 443 +/- 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1983

The pharmacokinetics and metabolism of ethinyl estradiol and its three sulfates in the baboon.

Ethinyl estradiol sulfates are major circulating metabolites of ethinyl estradiol (EE2); this is a relationship analogous to that of endogenous estrone and estrone sulfate. Because of the wide use of contraceptives containing EE2, the pharmacokinetics of its sulfate conjugates are of some importance. In previous studies of the intermediate metabolism of ethinyl estrogens we have shown that the baboon is an appropriate animal model. Accordingly, oral and/or intravenous doses of EE2 or each of its three sulfates were administered to castrate female baboons, and plasma levels of EE2 and its sulfates were studied by specific radioimmunoassay or radioisotope counting. After intravenous administration of EE2, the 3-sulfate and the 3,17-disulfate are the major circulating metabolites. After oral dosage administration, the 3-glucuronide and, in some cases, the 3,17-diglucuronide also become important. After intravenous administration, about twice as much of the drug exists in the sulfate as in the free form, as reflected by the areas under the plasma level curves. The bioavailability of orally administered EE2 was about 60%, confirming the presence of a substantial first-pass effect. Hydrolysis at the 17-position occurs when EE2-17-sulfate is administered orally but appears not to occur with intravenous administration. EE2 and the three sulfates, given intravenously, exhibited two-compartment open-model kinetics. The elimination phase half-lives of all four compounds were similar, ranging from 8.8 to 11.2 hours. The area under the plasma level curve of EE2 resulting from the intravenous administration of the 3-sulfate was approximately 8% of the total area under the plasma level curve of both EE2 and EE2 sulfates. The ratio of the area under the plasma level curve of sulfates resulting from 3-sulfate administration compared to the other two sulfates was approximately 0.3, reflecting the existence of other metabolic pathways for its disposition.

Administration, Oral↗
PubMed1983

The effect of estrogen antagonism on progesterone production in early pregnancy in the baboon (Papio cynocephalus).

These studies were designed to investigate the role of estrogen on progesterone production in early pregnancy in the baboon, when the contribution of the corpus luteum and placenta has not been established. Oral administration of the estrogen antagonist MER-25 at two dosage levels (15 and 30 mg/kg/day) to the pregnant baboon from days 35 to 55 after conception results in a decline in peripheral plasma levels of progesterone within a few days and persists for at least 20 days after the termination of treatment with no effect on plasma estradiol levels. The same study was done with the use of a different estrogen antagonist, trioxifene mesylate (5 mg/kg/day), and there was no effect on plasma progesterone, although a transient depression in plasma estradiol was evident. These actions may be due to an inherent estrogenicity of trioxifene. In preliminary studies an effect of these estrogen antagonists on placental size and morphology has been observed. Estrogen deprivation in early pregnancy of the baboon results in a depression in plasma progesterone and indicates a placental requirement for estrogen in progesterone product at this stage of pregnancy.

Abortion, Spontaneous↗
PubMed1983

Plasma androgens during early pregnancy in the baboon (Papio cynocephalus).

Time-mated baboons (n = 8) were bled throughout the luteal phase of the cycle of conception, and an equal number of nonpregnant animals were studied as controls. A significant increase in plasma testosterone and androstenedione was seen in the cycle of conception prior to expected menses, whereas the levels in nonpregnant baboons were unchanged throughout the luteal phase. Plasma testosterone and androstenedione continued their rise in three pregnant baboons sampled between days 16 and 33 of gestation. In an additional three baboons bled at 4-day intervals from day 35 through day 75, there was a further increase to about day 40, but by day 50 the androgen levels had declined to nonpregnant luteal phase levels and remained constant. Treatment with human chorionic gonadotropin during the nonpregnant luteal phase caused increases in both testosterone and androstenedione. Removal of the ovary bearing the corpus luteum at day 20 of gestation resulted in abortion and a sharp drop in plasma progesterone and estradiol. One baboon had a dramatic decline of the elevated plasma androgen following oophorectomy, while another that did not have elevated androgen levels showed only a trivial decline. Pregnancy continued in two baboons in which the corpus luteum-bearing ovary was removed at day 25 or day 30. There was only a slight drop in plasma progesterone postoperatively and a rapid return to normal levels. A similar decline, with a more gradual recovery, was noted in plasma estradiol and androgen levels. In one animal the androgen levels were increased by about day 40 and subsequently declined by day 50, just as did the androgens of unoperated pregnant baboons. Estrogen administration in early pregnancy causes a suppression of the normal increases in plasma estradiol and androgen levels.

Androgens↗
PubMed1983

The effect of testosterone on human chorionic gonadotropin-stimulated ovarian steroidogenesis in vivo in the baboon (Papio cynocephalus).

We have studied the effect of exogenously induced hyperandrogenism on the ovarian response to human chorionic gonadotropin (hCG) in the baboon. Normally cycling baboons were treated with increasing daily doses of hCG for 5 consecutive days from day 10 of the luteal phase (n = 5). Hyperandrogenic baboons received the same hCG regimen 1 hour after a Silastic capsule containing crystalline testosterone (T) had been implanted under the skin (n = 3). Control animals received an empty Silastic capsule (n = 8). All baboons were bled on alternate days from days 6 to 20 of the luteal phase, and daily during hCG treatment. T capsules induced immediate hyperandrogenism, with T levels several times greater than normal luteal phase levels. The use of hCG resulted in an increase in plasma progesterone within 24 hours and levels gradually declined thereafter. Estradiol increased rapidly and remained elevated during hCG treatment. In the presence of elevated T levels, hCG had a significantly reduced effect on the magnitude and duration of plasma progesterone increase. The effect of hCG on plasma estradiol levels was virtually eliminated in hyperandrogenic baboons. This study seems to demonstrate a direct inhibitory effect of T on ovarian steroidogenesis in vivo and may explain the ovarian changes that occur in hyperandrogenic women.

Animals↗
PubMed1983

Developmental patterns of serum luteinizing hormone, gonadal and adrenal steroids in the sooty mangabey (Cercocebus atys).

Serum levels of luteinizing hormone (LH), testosterone, dehydroepiandrosterone sulfate (DHAS), androstenedione and cortisol were determined in multiple samples from 86 sooty mangabeys of varying ages (0-17 years). Testosterone, androstenedione, DHAS and cortisol were measured by radioimmunoassay; LH was determined by in vitro bioassay. Serum LH concentrations were elevated in neonates (less than 6 months) and in animals older than 72 months of age. The higher LH levels were associated with increased circulating concentrations of testosterone in males but not females. The pubertal rise in serum testosterone at approximately 55-60 months of age in males was coincident with rapid body growth. No pubertal growth spurt was observed in females. Serum levels of androstenedione and DHAS were highest during early postnatal life (less than 6 months) with androstenedione exceeding 600 ng/dl in males and 250 micrograms/dl in females, but declined rapidly in both sexes to a baseline of 150 ng/dl by 19 months of age. Serum androstenedione did not fluctuate significantly in adult animals. The pattern of age-related changes in serum DHAS paralleled those of serum androstenedione, whereas serum cortisol values did not change significantly with age. Developmental changes in serum LH, testosterone and body weight suggest that the sooty mangabey matures substantially later than the rhesus monkey. The pattern of serum gonadal and adrenal steroids during sexual maturation is similar to that seen in the baboon with no evidence of an adrenarche.

Aging↗
PubMed1982

Steroid effects on relaxin secretion in the rat.

These studies were performed to determine if estrogen and/or androgens are involved in the regulation of relaxin secretion in the pregnant rat. Animals were hysterectomized at Day 15 of pregnancy and either untreated or given a) a subcutaneous Silastic capsule containing crystalline testosterone, b) a subcutaneous Silastic capsule containing crystalline dihydrotestosterone, or c) daily subcutaneous injections of 100 micrograms estradiol. A group of sham-operated animals served as controls. Serum samples taken at Days 14, 16, and 18 of pregnancy were assayed for relaxin and progesterone. Treatment with either estradiol or testosterone attenuated the decline in serum relaxin and progesterone concentrations observed following hysterectomy, whereas dihydrotestosterone (a nonaromatizable androgen) had no effect upon either relaxin or progesterone levels. These results suggest that estradiol and testosterone, previously implicated in the control of luteal progesterone production, also stimulate luteal relaxin secretion. The mechanism by which testosterone stimulates relaxin secretion is probably via its aromatization to estradiol within the corpus luteum.

Androgens↗
PubMed1982

Pubertal endocrinology of the baboon: elevated somatomedin-C/insulin-like growth factor I at puberty.

Previous data suggested an increase in the rate of weight gain and linear growth in the baboon between 3 and 4 yr of age, similar to the pubertal growth spurt in man. In this cross-sectional study, radioimmunoassayable concentrations of somatomedin-C/insulin-like growth factor I(SM-C/IGF-I) were compared in prepubertal (less than 3 yr), pubertal (3-4 yr), and adult (greater than 10 yr) animals. SM-C/IGF-I concentrations in prepubertal males (0.97 +/- 0.10 U/ml) were low and were not different from those in prepubertal females (0.98 +/- 0.15 U/ml). Between 3 and 4 yr, SM-C/IGF-I increased significantly in both sexes (8.87 +/- 0.74 and 5.27 +/- 0.52 U/ml, male and female, respectively) and decreased (5.92 +/- 1.2 and 2.75 +/- 0.13 U/ml, respectively) in animals greater than 10 yr of age. Sex differences were significant in the 3- to 4-yr-old animals (male greater than female, P less than 0.001). The pubertal elevation in SM-C/IGF-I concentrations is coincident with increases in indices of somatic growth and sexual maturation in the baboon. These and other data suggest that this animal may be an appropriate model for studies to define hormonal mechanisms of pubertal growth.

Animals↗
PubMed1982

The luteolytic and abortifacient potential of an estrogen-bromergocryptine regimen in the baboon.

Administration of 1 mg of estradiol benzoate (E2B) daily to normally cycling baboons on days 6, 7 and 8 after ovulation significantly shortens the luteal phase to 13.8 +/- 0.3 days (n = 5) from 16.0 +/- 0.6 days (n = 8) in vehicle-treated controls, and causes an early decline in plasma progesterone concentration. When 1 mg/kg bromergocryptine (CB-154) was administered twice daily in combination with the E2B treatment, there was an earlier depression of plasma progesterone and a further shortening of the luteal phase to 12.3 +/- 0.5 days (n = 4). In five pregnant baboons, the E2B/CB-154 treatment initiated on postconception day 20 produced a substantial depression of plasma progesterone, followed by a posttreatment rebound to control values, without apparent effect on the pregnancy. In both cycling and pregnant baboons, this dose of CB-154 produced a significant and sustained reduction in plasma prolactin levels.

Abortifacient Agents↗
PubMed1981

Evaluation of STS-557 as a postcoital contraceptive in the baboon.

A postcoital interceptive action of STS-557, a synthetic progestin, has been reported in the mouse, rat, and baboon. In the present study we reinvestigated the effects in the baboon with a modification of the original protocol: prolongation of the mating period from 6 to 48 hours. The time of mating was determined by observation of the perineal sex skin and the pattern of plasma estradiol in the periovulatory period. STS-557 (0.4 mg) was administered 6 hours after the initiation of mating, which was continued for an additional 42 hours. Controls received an empty gelatin capsule in the same mating protocol. Conception rate in the control baboons (n = 20) was 25%; in the STS-557-treated baboons (n = 18) it was 22%. There was also no difference in the pattern of plasma estradiol and progesterone in control versus treated baboons, either in pregnant or in nonpregnant animals. All pregnancies were normal. In light of the earlier report of effective postcoital action in the baboon from a single administration of STS-557 after a breeding period limited to 6 hours, our results indicate that the effect of a single dose is brief, and may not be clinically useful.

Animals↗
PubMed1981

Pubertal endocrinology of the baboon: adrenarche.

The concentration of the adrenal steroids dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHA-S) was measured by radioimmunoassay in plasma of 134 baboons (Papio cynocephalus) from 0 to 17 yr of age. Plasma androstenedione (delta 4-A) was also measured in 289 baboons encompassing the same age range. The concentration of DHA was persistently high from birth to adulthood, exceeding 700 ng/dl at all ages. This differs markedly from the human pattern in which DHA concentrations fall below 50 ng/dl following regression of the fetal adrenal. Plasma DHA-S declined rapidly during the first 2 yr of life, causing a significant age-related decline in the ratio of DHA-S:DHA, a pattern not seen in man. Plasma delta 4-A declined during the first 3 yr, but remained greater than 100 ng/dl. delta 4-A then rose sharply at age 4, the time of gonadal maturation in the baboon. Thus, the baboon differs from man primarily in the persistent elevation of plasma DHA and delta 4-A prior to puberty. It remains to be determined whether this difference reflects fundamentally different mechanisms regulating adrenal androgen secretion or merely the closer temporal juxtaposition of fetal adrenal regression and adrenarche due to the more rapid sexual maturation of the baboon.

Aging↗