Plasma Concentrations of Testosterone in the Male Dog and Plasma Testosterone Profile Following Single Intramuscular Injection of HCG

The spontaneous variation in plasma testosterone was studied in 4 dogs in a 24 h period. Blood samples were taken with 1½ h interval. A variation of 26–62 % was found in the plasma testosterone concentration and the values ranged from 2.7–15.6; 0.7–10.4; 4.2–17.3; 8.7–23 nmol/l. No effect of intramuscular injection of 150 i.u. HCG could be seen on the plasma testosterone levels in samples taken 5, 10, 20 or 30 min post injection. Thereafter plasma testosterone levels increased to reach levels equal to peak concentration in the control period 1½ h post injection. The variation in the plasma testosterone concentration 1½, 3 and 4½ h post HCG injection was reduced to 8.95 ± 2.8 % (mean ± s). Plasma testosterone in a sample taken 3 h after HCG injection might thus be indicative of a Leydig cell dysfunction in the dog. An additional increase (P < 0.001) in plasma testosterone levels was observed 21–30 h post injection. Thereafter levels of testosterone fell to pre-stimulation values.     

The Immediate Effect of HCG Upon Plasma Testosterone Levels in the Bull

No effect of HCG upon the plasma testosterone level in 16 bulls was seen the first 5 or 15 min after injection. In 8 bulls receiving 750 or 1500 i.u. HCG by intravenous injection a lag time of 30 min occurred before plasma testosterone response could be measured. The high plateau level of plasma testosterone concentration was reached approximately 1 h after injection. Following intramuscular injection of 750 i.u. or 1500 i.u. HCG a lag time of 45–60 min was observed for the testicular response measured as elevated plasma testosterone level. The high plateau levels of plasma testosterone in these bulls were reached approximately 1½ h post injection.     

Diurnal variations of serum testosterone levels in intact and gonadectomized male and female rhesus monkeys.

A radioimmunoassay for serum testosterone which does not require chromatographic separation was used to measure the diurnal variations in intact and orchidecomized males and intact and ovariectomized females. The intact male rhesus monkey shows a distinctive diurnal variation in serum levels of testosterone characterized by lower values during the day and a marked increase in the early evening (1900-2200 hr). The testosterone levels remain high throughout most of the lights-off period in the intact male. In contrast to the intact male, the markedly lowered serum levels of testosterone in the orchidectomized male were higher during the day and consistently showed a nadir during the early evening (2000-2200 hr). The evening nadir of testosterone levels was 51.0% lower than the 24-hr mean whereas the maximum serum level was 46.4% higher. A similar circadian pattern of testosterone was seen in both the intact and ovariectomized females. The testosterone values were higher during the day and consistently showed a nadir during the early evening. These results suggest that the adrenal secretion of testosterone varies in a diurnal pattern characterized by an early evening nadir. This adrenal pattern is overshadowed by a much larger gonadal rhythm in the intact male.     

Plasma Cortisol in the Horse,Diurnal Rhythm and Effects of Exogenous Acth

Peripheral blood plasma Cortisol concentration and its diurnal variation was measured in 4 horses. Mean concentration of Cortisol during 24 hrs. was 42 ng/ml (s ± 20 ng/ml). Peak values occurred at 6 a.m. and the lowest values were observed at about 6 p.m. (mean 65 ng/ml and 20 ng/ml, respectively). Long-acting ACTH at a dose of 150 i.u. was given by intramuscular injection to the 4 horses. Peak Cortisol concentrations markedly exceeding the prestimulation level were obtained between 2 and 4 hrs. after injection. During the immediate 24 hrs. after these peaks, the mean Cortisol level was markedly lower and the cyclic variation out of phase with the basal diurnal pattern. After a gradual adjustment during the second postinjection day, no differences could be seen between the 2 patterns on day 3 after injection.     

Plasma estradiol concentrations and effect of HCG on plasma estradiol and testosterone in normal subjects and patients with endocrine disorders.

Plasma estradiol concentrations were determined by radioimmunoassay in various endocrine disorders using antiserum to estradiol-17beta succinyl bovine serum albumin. Clinical significance and diagnostic value of plasma estradiol were assessed in hypothalamic-pituitary, adrenal and gonadal disorders. In general, estradiol concentration was correlated well with the degree of sexual maturity and was of great diagnostic use. Plasma estradiol in females mainly originated from the ovary, while the testis is the principal source of estradiol in males. The adrenal gland seemed to play a minor role as a source of estradiol at least in normal males and females. The role of estradiol in gynecomastia and in liver disease was also investigated. More than a half of the cases with gynecomastia had elevated concentrations of plasma estradiol, which probably explains the pathogenesis of this manifestation. Cirrhotic patients showed frequently hyperestrogenemia probably due to delayed disappearance of estradiol. In the study of stimulation with human chorionic gonadotropin (HCG), 3,000 IU daily for three days in ten normal men, the peripheral concentrations of esradiol showed maximum and fourfold increases 24 hours after the 1st injection of HCG. The testosterone levels, on the other hand, increased stepwise and reached a maximum of about two times preinjection levels 24 hours after the 3rd injection. In gonadal disorders, HCG produced various patterns of plasma estradiol and testosterone in accordance with the gonadal conditions and dissociated response patterns of both sex hormones were frequently found. The determination of plasma estradiol was useful in the study of the function of not only the ovary, but also the testis and the simultaneous measurement of plasma estradiol and testosterone after HCG administration presented interesting informations about pathophysiology of gonadal disorders.     

Diurnal changes in plasma prolactin during the last one third of pregnancy in the baboon

Previous studies in our laboratory revealed that daily plasma prolactin (Prl) levels were higher in the evening than in the morning in the pregnant baboon suggesting a diurnal variation. The goal of this study was to examine in more detail the diurnal alterations in plasma Prl levels. A tethered pregnant baboon model was utilized for these studies. Hourly venous blood samples were taken from 0700 to 2400 hr (n=10) or until 0700 hr the following day (n=5). The studies were performed at various days of pregnancy from day 135 until delivery. Plasma samples were analyzed for Prl by radioimmunoassay. A surge in plasma Prl was detected, starting around 1500 to 1600 hr and lasting for 3 to 5 hr. The surge occurred before the lights went off in the colony (1800 hr). Baseline Prl levels were higher in animals < 15 days before delivery compared to those > 15 days before delivery (P < 0.05). In contrast, no differences were found in the average peak Prl values between these two groups of animals. In summary, in the pregnant baboon during the last one-third of pregnancy plasma Prl surges, beginning around 1500 to 1600 hr and lasting for 3 to 5 hr. Less than 15 days before delivery the mean baseline Prl levels are higher compared to animals greater than 15 days before delivery.     

The influence of dehydroepiandrosterone on basal and gonadotrophin-stimulated testosterone secretion by Mongolian gerbil interstitial cells incubated or superfused in vitro

1. Testosterone secretion by Mongolian gerbil interstitial cells incubated in the absence of HCG linearly increased with cell concentration (1 x 10(5) cells: 0.6 ng/4 hr, 10 x 10(5) cells: 8.0 ng/4 hr). Addition of 100 mIU HCG resulted in a drastic increase of testosterone secretion which was linear between concentrations of 1 x 10(5) and 4 x 10(5) cells. 2. Compared to HCG-stimulated testosterone release, secretion was significantly higher by cells incubated with 60-100 ng DHEA. 3. During the 4-hr incubation period, 53-69% of added progesterone and 72-88% of added dehydroepiandrosterone (DHEA) were converted to testosterone by cells freshly prepared or stored for 1-3 days at 4 degrees C. On the other hand, prolonged storage at 4 degrees C resulted in a marked decrease of HCG-stimulated testosterone secretion. 4. Testosterone secretion by interstitial cells superfused in vitro increased with the length of HCG (100 mIU/ml) application from 0.08 to 0.22 ng/10(6) cells/min (10 and 60 min, respectively). A much faster and pronounced elevation was found when cells were stimulated with DHEA (200 ng/ml: 0.06-0.80 ng/10(6) cells/min, 0 and 20 min, respectively). 5. After interstitial cells have been stimulated with a DHEA (200 ng/ml) pulse for 30 min and then superfused with medium only for an additional 30 min, testosterone secretion remained significantly elevated and could not be further stimulated by superfusing medium which contained as much as 100 mIU/ml HCG.     

Bioavailability and LH-suppressing effect of different testosterone preparations in normal and hypogonadal men.

The therapeutic effectiveness of intramuscularly administered testosterone esters and free testosterone in suppositories was investigated by the measurement of plasma testosterone and LH levels after administration to normal and hypogonadal men. Testosterone levels were elevated above the lower physiological limit for 1 day after 25 mg testosterone one propionate, for 2 days after 50 mg testosterone propionate and for 14 days after 250 mg testosterone oenanthate. LH levels were suppressed for the corresponding periods. Elevated plasma testosterone and suppressed LH levels were maintained by testosterone suppositories (3 x 20 mg for 5 days).     

醋酸棉酚对大鼠睾丸HCG反应性及其受体功能的影响

给大鼠灌服醋酸棉酚30 mg/kg/d,每周6次,持续4周。给药2周后,血浆睾酮水平显著下降并持续至第4周,同时间质细胞呈萎缩性改变。醋酸棉酚明显抑制成年大鼠对HCG反应性,使睾丸LH/HCG受体亲和力下降,受体数目略有减少。结果提示,醋酸棉酚抑制大鼠睾丸酮的产生及降低成年大鼠睾丸对HCG的反应性,推测其机制是由于醋酸棉酚干扰了睾丸HCG受体功能而造成的。     

Hormone response of dairy cows with ovarian cysts after treatment with HCG or GnRH

Twenty lactating Holstein and Guernsey cows, diagnosed by rectal palpation as having ovarian cysts, were randomly divided within breed into two groups to receive either a single intramuscular injection of 100 μg of synthetic gonadotropin releasing hormone (GnRH) or an intravenous injection of 10,000 IU of human chorionic gonadotropin (HCG). The objective was to compare hormonal and clinical changes in cows with ovarian cysts following treatment with GnRH and HCG. Eight of ten and nine of ten cows given either GnRH and HCG, respectively, responded to treatment and subsequent fertility was not different between the two groups. Pre-injection plasma levels of LH, progesterone, and estradiol were highly variable. Mean plasma levels of LH, progesterone and estradiol did not differ between groups either following treatment (days 1–17 post-treatment), at the subsequent estrus, or during days 1–13 following the subsequent estrus. Mean LH levels did not differ significantly on the days either post-treatment or post-estrus except that levels were higher (P < .01) at the subsequent estrus as compared to the other days. Mean progesterone levels increased after treatment with either GnRH or HCG and were higher on days 5, 9 and 13 post-estrus and post-treatment as compared to the subsequent estrus. Mean levels of estradiol were higher (P < .05) at the subsequent estrus than any other time post-treatment or post-estrus. No other days were significantly different. In conclusion, GnRH and HCG are effective treatments for ovarian cysts in cattle. Endocrine response on days following treatment are similar for both compounds.     

Basal and HCG-stimulated testosterone production by interstitial cells of the Mongolian gerbil (Meriones unguiculatus)--I. Influence of preincubation length, medium composition and temperature

In the absence of HCG, production of testosterone by whole testes superfused in vitro was quite constant during the 5-hr superfusion period. Addition of 23-184 mIU/ml HCG caused a significant increase of testosterone production which was apparent from 30 min after start of superfusion. Basal and HCG-stimulated testosterone production by whole testes was significantly higher (400, 1950 ng/testis/5 hr, without and with 100 mIU HCG) than by isolated cells (200, 1350 ng/testis/5 hr). Incubation of isolated interstitial cells in medium 199 supplemented with fetal calf serum (FCS), (N-2-hydroxyethylpiperazine-N-2-ethanesulphonic acid, HEPES) and 3-isobutyl-methylxanthine (MIX), and in medium 199 without FCS, HEPES or MIX, gave similar testosterone responses. While centrifugation at 8000 g for 2 min drastically diminished testosterone formation by isolated interstitial cells, production was similar by cells incubated in either 0.5, 1.0 or 1.5 ml medium. A significant decrease of testosterone synthesis by isolated interstitial cells was found when cells were stored at 4 degrees C for 2 days and then were incubated at 35 degrees C for 6 hr without or with 1-1000 microIU HCG. While isolated interstitial cells incubated at 5 degrees C did not produce testosterone at all, testosterone production increased to 49.5 +/- 3.9 ng/10(5) cells (30 degrees C) and 24.1 +/- 1.1 ng/10(5) cells (40 degrees C), respectively. HCG-stimulated testosterone production was maximal when interstitial cells were incubated at 34 degrees C.     

Frequency of cocaine administration affects behavioral and endocrine responses in male and female Fischer rats.

Accumulating evidence has shown disparate behavioral responses to cocaine in male and female rats. To date, there is a lack of understanding of how cocaine administration frequency affects sexually dimorphic behavioral responses. In the present study we investigated the behavioral and endocrine responses to single (1 x 15 mg/kg) and "binge" (3 x 15 mg/kg) cocaine administration in male and female Fischer rats. Overall, females showed a more prolonged and robust behavioral response to both acute and "binge" pattern cocaine administration. Furthermore, sex-dependent behavioral topographies emerged during binge-pattern cocaine administration; female rearing activity increased across "binge" injections while ambulatory activity decreased. In contrast, male ambulatory and rearing behaviors remained constant across injections of "binge" cocaine. At the hormonal level, both single and "binge" pattern cocaine administration decreased testosterone levels in male rats. However, cocaine's modulation of testosterone levels was transient since testosterone levels were decreased by cocaine 30 min but not 3 hr following a single injection. In both male and female rats, "binge" cocaine increased plasma progesterone levels. However, acute cocaine administration increased progesterone levels transiently in only female rats. Our results show that pattern of administration affects both cocaine-stimulated behavioral and endocrine responses in male and female rats.     

Role of prostaglandin F2alpha in ovulation.

Using radioimmunoassay procedures, the levels of plasma, uterine and ovarian prostaglandin (PG) F2alpha, and those of plasma estradiol and progesterone were measured in intact, hysterectomized or ovariectomized immature female rats pretreated with PMS and subsequent HCG. Occurrence of ovulation was confirmed at 8 hours after the HCG administration not only in the intact rats but also in the hysterectomzied rats. The levels of plasma estradiol and progesterone, and of uterine and ovarian PGF2alpha rose with the PMS injection alone, but they did not reach the peaks before the HCG administration. Both plasma estradiol and uterine PGF2alpha showed a peak at 2 hours after the HCG injection. These peaks were antecedent 2 or 6 hours before the peaks of ovarian and plasma PGF2alpha, respectively. However, such increase of uterine PGF2alpha does not seem to be indispensable for ovulation, because ovulation could occur in the hysterectomized rats. The levels of ovarian PGF2alpha showed a high plateau from 4 to 8 hours after the HCG injection, and then rapidly decreased after ovulation. The levels of plasma PGF2alpha peaked not only in the intact rats but also in the hysterectomized rats at 8 hours after the HCG treatment. But in the ovariectomized rats, this plasma PGF2alpha peak at 8 hours disappeared and there was no statistical change of plasma PGF2alpha throughout the PMS-HCG treatment. Plasma progesterone gradually increased and reached the maximum at 10 hours after the HCG injection. These results conclude that the main source of increased plasma PGF2alpha during the ovulatory process induced with the PMS-HCG treatment is the ovary, and it is strongly suggested that a rapid increase of PGF2alpha in the ovary may play some important role(s) in the ovulatory process.     

慢性炎症因子在多囊卵巢综合征中的作用机制

目的通过构建多囊卵巢综合征(PCOS)大鼠模型,探讨慢性炎症在PCOS发病过程中的作用机制。方法皮下埋置17-炔诺酮硅胶棒联合皮下注射HCG(Bogovich法)诱导PCOS大鼠模型。测定血清肿瘤坏死因子-α(TNF-α)、睾酮(T)空腹血糖(FPG)及空腹胰岛素(FIns)水平。结果模型组于6d形成PCO大鼠,24d构建PCOS大鼠模型成功。模型组血清TNF-α,T,FIns,FPG,胰岛素抵抗指数(Homa-IR)均高于对照组,胰岛素敏感指数(ISI)低于对照组。结论 Bogovich法诱导PCOS大鼠模型是研究PCOS发病机制的理想动物模型,慢性炎症可能诱导IR参与PCOS的发生与发展。     

Steroid levels after intramuscular injection of radioactive estradiol-17beta, estrone, progesterone and testosterone in the bovine

Eight 2 year old Hereford cows from days 8 to 12 of the estrous cycle were injected intramuscularly with 5 ml of corn oil containing 5 mg of estradiol-17beta (two cows), estrone (two cows), progesterone (two cows) or testosterone (two cows). Each cow treated with estradiol received 494 microc of estradiol-17beta-6, 7 H3 and each cow treated with estrone received 492 microc of estrone-6, 7 H3. Each cow treated with progesterone or testosterone received 400 muc of H3 compound labeled in the 7 position. Total urine was collected by urethral catheterization of the cows treated with estrogens. Blood samples for plasma and serum were collected via jugular cannulae. Blood and urine samples from estrogen-treated cows were collected hourly for the first 24 hr, at 2 hr intervals for the next 26 hr, at 4 hr intervals for the next 12 hr and at 12 hr intervals until background was reached. Blood samples were collected hourly from 1 to 8 hr after injection from progesterone or testosterone-treated cows. Plasma and serum levels of radioactive estradiol-17beta, estrone, progesterone and testosterone were similar. Blood levels of radioactivity peaked at 2 hr post-injection in cows receiving estradiol-17beta and at 3 hr in cows receiving estrone. Blood levels of labeled estradiol-17beta and estrone were nondetectable by 54 hr and 83 hr, respectively. Peak urinary excretion of radioactivity was reached at 7 hr for estradiol-17beta and at 14 hr for estrone and nondetectable levels were reached by 95 hr for estradiol-17beta and 14 hr for estrone. At these times, 15.5% of the total dose of radioactive estradiol-17beta and 17.5% of the injected estrone had been excreted in the urine. Peak blood and urinary excretion levels were reached earlier for radioactive estradiol-17beta than for estrone, and excretion of estradiol-17beta was completed more rapidly. No difference was found in plasma and serum levels for any steroid studies; thus, endogenous steroid titers in blood plasma and serum are not different in the cow.     

Prolonged stimulation of adenylate cyclase activity and testosterone production by cholera enterotoxin with suppression of gonadotropin release in rats.

Endocrine effects of cholera enterotoxin (CET) on male gonads were investigated in normal and hypophysectomized rats. After intratesticular injection of 5 micrograms of CET in the bilateral testes of normal rats, serum testosterone concentration remarkably increased after 24 hr, remained significantly elevated for at least 3 days and returned to the control level in 7 days. Serum LH level decreased in the undetectable range after 1--3 days; serum FSH level also significantly decreased after 3 days. Both gonadotropin levels increased 28 days after the injection, when the CET-injected testis decreased in weight and was accompanied by marked loss of germinal cells. When 5 micrograms of CET was injected intratesticularly in the bilateral testes of hypophysectomized rats, adenylate cyclase activity of a CET-injected testis was remarkably stimulated after 6 hr, remained four times elevated for at least 3 days and returned to the control level in 7 days. In relatively good accordance with the increase in adenylate cyclase activity, testosterone content remarkably enhanced in the CET-injected testis. These in vivo data indicate that the intratesticular injection of CET prolongedly stimulates the adenylate cyclase activity of testicular cells including Leydig cells and increases testosterone production, and suggest that the prolonged enzyme stimulation results in the sustained elevation of serum testosterone concentration for at least 3 days, causing the stimulation of the negative feedback mechanism of hypophysealtesticular axis to decrease serum LH levels in the undetectable range.     

Effect of HCG on the interstitial cells and androgen production in the immature rat testis.

The effect on the interstitial cells in the immature rat testis of administration of HCG for different periods was correlated with testosterone plasma levels. Significant and progressive stimulation of mitosis was observed after 3 days of HCG treatment but stabilization occurred after 5 days. The numbers of precursor fibroblasts had increased by the 5th day and were still increasing by the 10th day of treatment. Numbers of Leydig cells were significantly greater at 5 and 10 days of treatment. Plasma testosterone showed a progressive and continuous increase in all groups. The increase in Leydig cell number is considered to be due to a combination of increased stimulation of mitoses in Leydig cells and differentiation of precursor fibroblasts. Mitosis seems to precede fibroblastic differentiation, but the latter continues when mitotic changes have stabilized. The elevation of plasma testosterone concentrations is probably due firstly to the stimulation of the existing Leydig cells and then to the increase in the number of hormone-secreting cells.     

Effect of photoperiod on the diurnal rhythm of plasma testosterone, dihydrotestosterone and androstenedione in mature male chickens

1. The effects of different photoperiods on the concentrations of plasma androgens, testes weight and on the diurnal rhythm of plasma testosterone (T), dihydrotestosterone (DHT) and androstenedione (A) in mature, single comb White Leghorn male chickens were studied. 2. Birds were exposed to either 14 hr of light (lights on at 0600-2000 hr) or to 24 hr of light per day. 3. Blood samples were collected from birds in both groups at 3-hr intervals and plasma levels of T, DHT and A were measured using radioimmunoassays. Following blood collection, birds were weighed, killed and testis weights were recorded. 4. Under 14 hr of light, there was a diurnal rhythm of T and DHT with hormone concentrations peaking at the end of the dark period. There was no obvious rhythm for A. Exposure to 24 hr of light abolished the diurnal rhythm found under 14 hr of light. 5. There was an increase not only in testis weights but also in body weight and hormone concentrations under 24 hr of light. 6. It was concluded that photoperiod plays an important role in controlling the concentration and rhythm of androgens in mature male chickens.     

Plasma Testosterone in Bulls

Levels of peripheral plasma testosterone and LH were studied in 4 bulls hourly during a 12 hr. sampling period at 5 times of the year. The average plasma testosterone levels were significantly lower in October (1.8 ng/ml, Ρ < 0.001) and December (2.5 ng/ml, Ρ < 0.05) than in February, June and August (3.5, 3.7 and 3.7 ng/ml respectively). LH showed a slight fluctuation during the day, with values ranging between 0.8 and 3.8 ng/ml, but underwent no significant seasonal variation. A significant increase in average plasma testosterone was observed 1 hr. after the LH peaks (P < 0.001).