Luteinizing hormone in the Kowari, Dasyuroides byrnei (Marsupialia:Dasyuridae), during the oestrous cycle and pregnancy, and the effects of gonadectomy in male and female

A heterologous double antibody radioimmunoassay has been validated for measurement of LH in plasma of a dasyurid marsupial. Basal concentrations in the oestrous cycle of female kowaris were in the range of 0.5-2.0 ng NIH-oLH-S19 mL-1. Many animals showed elevated LH concentrations (3.0-12.0 ng mL-1) between 8 and 15 days before oestrous but no pre-ovulatory surge was detected. Gonadectomy resulted in greatly increased concentrations of LH, and decreases in testosterone and progesterone concentrations in male and female respectively. In the female LH values ranged from 10-50 ng mL-1 but in the male LH values were greater than 50 ng mL-1.     

Inhibition of testosterone synthesis by ethanol: role of luteinizing hormone

The effects of acute ethanol intake (1.5 g/kg) on plasma testosterone and luteinizing hormone (LH) concentrations were examined in male Long-Evans rats. Ethanol decreased the serum LH concentrations by 21% and 42% 30 and 60 minutes after ethanol administration respectively. The testosterone concentrations decreased later (30 min: +8%; 60 min: -30%). The LH concentrations were highly correlated with subsequent (60 min later) testosterone concentrations (LH30min: r = .688, p less than 0.001, n = 25; LH60min: r = .678, p less than 0.001), but less so with concurrent testosterone concentrations (30 min: r = .187, N.S.; 60 min: r = .552, p less than 0.004). To further test the influence of LH, naloxone (11 mg/kg) was administered, which elevated the LH levels within 30 min by 103% in controls. Naloxone also increased serum LH concentration by 34% in ethanol-treated rats at 30 min, but these animals nevertheless had lower (p less than 0.01) testosterone levels at 60 min than did control animals without naloxone and ethanol treatment. It is concluded that although ethanol-induced changes in serum LH levels may play a role in the decrease of serum testosterone concentrations in rats, there are also other mechanisms by which ethanol may produce these effects.     

Discriminatory effect of anti-Pr-beta-hCG-TT antibodies on the neutralization of the biological activity of placental and pituitary gonadotropins.

In 2 test systems, serum from monkeys and human subjects immunized with an anti-human chorionic gonadotropin (hCG) vaccine, Pr-beta-hCG-TT, were analyzed for their capacities to neutralize hCG/luteinizing hormone (LH)-induced biological effects. hCG-induced ovulation was completely blocked by the monkey antiserum in mice, but the same amount of antiserum, and even 2-fold greater concentrations, did not reduce the number of ovulating animals when primed with ovine LH. Competency of both the immunized monkey and human sera to neutralize the hCG-induced testosterone production in Leydig cells was shown. All monkey and 7/12 human sera did not interfere with the human LH action on Leydig cells. 5 human sera, however, showed varying degrees of inhibition of human LH-induced sterodogesnesis by this sensitive Leydig cell bioassay. Nevertheless, these subjects maintained regular menstrual cycles, and serum progesterone levels during the luteal phase were consistent with ovulation. Normal hormone profiles were constructed from a subject whose serum had shown a fairly high degree of cross-reaction with human LH by the Leydig cell bioassay when estradiol, human LH, and progesterone levels were determined on different days throughout the menstrual cycle.     

Persistent disturbance of the hypothalamic-pituitary-gonadal axis in abstinent alcoholic men

AIMS: Testosterone synthesis in chronic alcoholics is affected by a variety of mechanisms. Little is known about the reversibility of these changes upon abstinence and available data on circulating hormone levels are incomplete and inconsistent. METHODS: Serum concentrations of free testosterone, total testosterone, and luteinizing hormone (LH) were determined in 18 male non-cirrhotic chronic alcoholics on days 2, 22, 82 and 127 of strictly controlled abstinence, as well as in a group of 20 healthy age-matched controls. RESULTS: Higher total testosterone concentrations were found in alcoholics on the second day of abstinence, as compared to controls (7.1 +/- 1.9 vs 5.6 +/- 1.4 ng/ml) and throughout the whole observation period. Correspondingly, free testosterone concentrations were increased over control levels on day 2 (40.0 +/- 12.1 vs 29.7 +/- 8.1 pg/ml) and stayed elevated in the presence of augmented concentrations of LH [4.5 U/l (range 1.6-9.5 U/l) vs 2.0 U/l (range 0.8-8.1 U/l)] for up to 127 days of strictly controlled abstinence. CONCLUSIONS: Sustained increases in serum free and total testosterone levels in the presence of inadequately raised LH concentrations point towards persisting disturbances of the hypothalamic-pituitary-gonadal axis in male alcoholics upon cessation of drinking.     

The effect of a synthetic progestin (R 2323) on gonadal and endometrial cells in vitro and in vivo

Gestrinone (R 2323) is a synthetic progestogen, and noteworthy agent for endometriosis treatment. The effect of this reagent on cultured cells from porcine granulosa, human endometrial and endometrial carcinoma origin was investigated concerning their hormonal activities and cell proliferations. Also, the effect of gestrinone on the serum levels of gonadotropins and gonadal steroids in patients with XY gonadal dysgenesis (Swyer's syndrome) and uterine myoma was studied. The monolayer cell colony established from the endometrial tissue fragments was positively stained by PAS similar to the secretory phase endometrium by 10 ng/ml gestrinone in the culture media. Endometrial carcinoma cells from a 65-year-old patient were proliferated by gestrinone at the concentration of 50 ng/ml in the culture media. The effect of gestrinone on the secretions of progesterone and estradiol-17 beta with or without hCG/testosterone from the cultured porcine granulosa cells was also investigated. Progesterone secretions were stimulated at the 50 ng/ml concentration of gestrinone, especially in association with hCG. Nonetheless, at the concentration of 500 ng/ml, those were inhibited. The secretions of estradiol-17 beta were stimulated by this reagent both with and without testosterone in dose-dependent manners. The effect of 25 mg gestrinone administration for 3 days on the levels of LH, FSH, progesterone and estradiol-17 beta in a patient with XY gonadal dysgenesis was as follows. Both LH and FSH levels gradually decreased, whereas estradiol-17 beta level was increased. The same dosage of this reagent was administered to a patient with uterine myoma on her menstrual days 7, 8, and 9.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of repeated hyperbaric exposures on the menstrual cycle: preliminary study

Two healthy female volunteers were subjected to hyperbaric air pressure of 5 ATA comparable to 130 feet of sea water (fsw) for 20 min 7 or 8 times during their menstrual cycles (experimental cycles). During the experimental cycles hormone assays for follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, and testosterone were performed before and after each dive on alternate days between the 5th and 11th cycle days (follicular phase), daily during the time ovulation was expected to occur, and on alternate days during the luteal phase; these were compared with the same assays throughout control cycles, during which the subjects were not pressurized. Periodic pressurization produced no significant changes in hormone patterns; ovulation was not inhibited and menstrual periods were unchanged.     

Effects of vitamin E deficiency and non-biological antioxidant (DPPD) on the function of the pituitary-gonadal axis of the rat

The effects of vitamin E deficiency on pituitary-gonadal function in rats and the preventive effects of N,N'-diphenyl-p-phenylene diamine (DPPD) administration were examined by measuring levels of pituitary and plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH), serum and testicular levels of testosterone, and affinity and receptor sites of FSH and LH in the testis by radioimmunoassay, at 180 days after feeding of a vitamin E-deficient diet and DPPD-administered diet. Light and electron microscopic examinations were also performed on the pituitary gland and testis. In the vitamin E-deficient rats, serum and liver alpha-tocopherol concentrations decreased significantly and erythrocyte hemolytic rate and serum and tissue malondialdehyde levels increased significantly. However, the increase of hemolytic rate and malondialdehyde concentration in the vitamin E-deficient rats was somewhat lessened by the administration of DPPD. In the vitamin E-deficient rats, the gonadotropic cells in the pituitary gland manifested accelerated secretory function indicated by enlargement of cells, development of Golgi apparatus and accumulation of secretory granules, while FSH and LH concentrations in the pituitary and serum were not affected by vitamin E deficiency. However, the testosterone concentrations in the plasma and testis were significantly lower in the vitamin E-deficient rats. The decrease of testosterone in plasma and tissue was prevented by the administration of DPPD, while the degeneration of seminiferous tubules was not completely restored by DPPD. It is concluded that DPPD can compensate to some degree for the lack of antioxidative activity due to vitamin E deficiency.     

Studies on ovarian and adrenal steroids at different phases of the menstrual cycle: III. Steroid and lutropin levels before and after the administration of a single contraceptive dose of depot-medroxyprogesterone acetate (DMPA)

Ovarian and adrenal steroids and biologically active lutropin were measured in peripheral plasma samples obtained from 5 normally menstruating women. Plasma samples were collected every 3 h for a period of 39 hours in the periovulatory period of a pretreatment (control) cycle and then 16 and 54 days after a single i.m. injection of 150 mg of depot-medroxyprogesterone acetate (DMPA).Sixteen days after DMPA administration, the levels of estradiol, progesterone, 17-hydroxyprogesterone, and lutropin were reduced to early follicular phase levels. No further decrease was found in 17-hydroxyprogesterone and lutropin levels; however, an additional decrease occurred in the levels of estradiol and in the “morning” levels of progesterone 54 days after the administration of DMPA.Furthermore, the levels of pregnenolone, androstenedione, testosterone and dihydrotestosterone were significantly diminished in all samples collected after the administration of DMPA.Fifty-four days following the administration of DMPA, the levels of cortisol and 17-hydroxypregnenolone were significantly reduced.The administration of DMPA did not interfere with the circadian rhythm of cortisol, pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 17-hydroxyprogesterone, and androstenedione levels. A significant circadian rhythm was also found in testosterone (after 16 days) and lutropin (after 54 days) levels. No circadian variation was found in estradiol, progesterone and dihydrotestosterone levels.     

Insensitivity of synthetic LRF in LH-release of rhesus monkey

Serum concentrations of LH were measured daily by radioimmunoassay throughout the menstrual cycles of 8 rhesus monkeys (Macaca mulatta). A midcycle LH surge was observed in all animals studied on days 10 to 17 (mean 13.5) of the cycle with an increase of 2- to 7-fold (mean 5) from the levels of follicular and luteal phase. The apparent ovulation was confirmed by the increase of serum progesterone after midcycle LH surge in all animals.

The effect of synthetic LH-releasing factor (LRF) on the release of LH was then studied in 7 rhesus monkeys with different endocrine milieu, but no detectable response was observed with a single intravenous administration of 1 to 50 g which has been shown to be effective in humans. This disparity was unexpected and suggests a species difference in responsiveness to the synthetic decapeptide between monkeys and humans.     

Hormonal effects of the 300 μg norethisterone (NET) minipill: 2. Daily gonadotrophin levels in 43 subjects during a pretreatment cycle and during the second month of NET administration

The peripheral plasma levels of immunoreactive follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) were measured daily in 43 normally menstruating women during a pretreatment (control) cycle and during the second month of daily administration of the 300 μg norethisterone (NET) minipill. In addition, the levels of biologically active LH were also determined in 29 of the 43 subjects.

As described in detail in the first paper of these series (1), the 43 women studied exhibited four distinctly different types of ovarian reaction to NET, as indicated by the daily estradiol and progesterone levels. Seven women (16 %) showed neither follicular, nor luteal activity (group A), 10 women (23 %) exhibited a cyclic follicular activity, but no luteal function (group B), 9 women (21 %) had normal follicular function, but insufficient luteal activity (group C), and 17 women (40 %) had estradiol and progesterone levels undistinguishable from those seen in a normal ovulatory cycle (group D).

Administration of the NET minipill did not influence the mean FSH lvel of cycle days 1–6, or those of 3 to 7 days before the LH peak; it slightly decreased the mean luteal phase FSH level in group C, but no in group D, and markedly suppressed the FSH peak value in all groups. There was no difference in this respect between women exhibiting different types of ovarian reaction. Similar to its effect on FSH, the administration of NET did not diminish the mean LH levels of days 1–6, those of 3 to 7 days before the LH peak, or of the luteal phase, but greatly suppressed the LH peak. Again, there was no difference in LH levels during NET administration among women showing different types of ovarian response to the drug. On the other hand, significant differences were found in the LH levels of the pretreatment (control) cycles of the various groups. The mean levels of LH both during days 1–6 and during the luteal phase of the pretreatment cycles were significantly lower in women in whom the minipill subsequently abolished all lutaeal activity (groups A+B) than in women exhibiting different degrees of luteal function (groups C+D). Hence the NET minipill will preferentially inhibit ovulation in women exhibiting relatively low tonic LH-levels in untreated cycles.

The results of the daily LH bioassays were in good agreement with those of the radioimmunoassays.

In the majority of women who exhibited normal (“ovulatory”) estradiol and progesterone profiles during NET administration, the preovulatory FSH, and especially LH peaks were below the lower limit of normal values, and in several instances, normal estradiol and progesterone profiles were found in the virtual absence of any FSH and LH surge.

It is concluded that ovarian suppression by the NET minipill is unrelated to the degree of inhibition of FSH and LH secretion as far as this is reflected by their peripheral levels measured daily.     

Ethanol-induced alterations in Rab proteins: possible implications for pituitary dysfunction.

Chronic exposure of pubertal male rats to ethanol results in a decline in serum testosterone, increased gonadotropins, pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) content, and decreased or inappropriately normal serum LH and FSH levels, suggesting impaired secretory release of gonadotropins. The molecular mechanisms behind this disorder are undefined, but a disruption of vesicle-mediated secretory processes is possible because intracellular protein trafficking pathways are involved in secretion of glycoproteins such as FSH and LH. Because small GTP-binding proteins of Rab family have been implicated as key regulators of membrane and protein trafficking in mammalian cells, this study was designed to test if ethanol-impaired pituitary FSH and LH secretion is associated with changes in Rab proteins, particularly Rab1B, Rab3B, Rab6, and Rab11. Male Sprague-Dawley rats 35 days old were pair-fed a Lieber-DeCarli diet with ethanol or without ethanol for 5 to 60 days. After ethanol exposure, serum testosterone levels decreased while LH and FSH were inappropriately unchanged. Immunohistochemical staining showed decreased Rab1B, Rab3B, and Rab11 protein levels in ethanol-treated pituitaries. Immunoblotting showed that ethanol induced a transient reduction in Rab6 after 5 days of ethanol exposure, whereas Rab3B decreased after 20 days, Rab11 after 30 days, and Rab1B after 60 days. Despite these changes in Rab proteins, mRNA levels were unaffected by ethanol exposure. We concluded that reductions in key Rab proteins may lead to altered vesicle trafficking and may play a role in disruption of pituitary FSH and LH secretion caused by ethanol.     

Immediate postabortal contraception with Norplant: levonorgestrel, gonadotropin, estradiol, and progesterone levels over two postabortal months and return of fertility after removal of Norplant capsules

Six Silastic levonorgestrel-releasing capsules, Norplant, were introduced subcutaneously into the ventral aspect of the left forearm or upper arm of thirteen patients immediately after first trimester pregnancy termination. Blood samples were taken twice a week over two months after abortion and from one subject over one month after removal of Norplant capsules. Plasma concentrations of levonorgestrel were measured by radioimmunoassay and the effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. If removal of Norplant capsules took place because of planning pregnancy, the subjects were asked to inform us if they had become pregnant. During the first month after abortion the mean levonorgestrel concentration (489 pg/ml) was statistically significantly higher than during the second month (237 pg/ml). The mean estradiol values fell to prefollicular levels within four days, remaining a little suppressed. The mean progesterone concentrations were below 2 ng/ml three days after abortion. Three subjects had a transient increase in plasma progesterone concentrations nine days after abortion. Thereafter no ovulatory progesterone concentrations were seen. The LH concentrations ranged within normal values of the follicular phase and FSH values were just beneath the lower limit of follicular phase FSH values, apart from a few peaks, indicating mild suppression. After removal of Norplant capsules, progesterone concentrations increased to ovulatory levels fifteen days after removal. The Norplant capsules were removed from two subjects because of planning pregnancy and they delivered healthy babies 9.5 and 12.5 months after removal.     

Effect of Sexual Maturity on Testicular Injury Subsequent to Procarbazine Administration in Rats

The present study examined the effect of age on various aspects of Leydig cell and Sertoli cell function in Sprague-Dawley rats administered procarbazine. Procarbazine was administered intraperitoneally to Sprague-Dawley rats aged 14, 24, and 60 days in 3 weekly injections of 200 mg/kg. Animals were sacrificed 1 week after the last injection. Severe impairment of spermatogenesis was evident in all animals. Sertoli cell function, as assessed by total testicular ABP content, was not significantly different between procarbazine-treated animals and controls in any age group. On the other hand, procarbazine administration resulted in a 60% reduction in total intratesticular testosterone content in the 14-day-old rats but not in the 24- or 60-day-old animals. Serum testosterone was significantly reduced by 50% in the group of 14-day-old animals but not in the other age groups. Serum LH values were not significantly changed from control levels in any age group. Testicular content of Fe, Zn, Mn, and Cn were unaltered by procarbazine administration in any age group. Since serum LH and testicular cation content were not affected by procarbazine treatment, the significant decreases in serum and testicular testosterone in 14-day-old animals after procarbazine administration may indicate a direct age-dependent effect of procarbazine on Leydig cell function.     

Subjective assessment of sexual dysfunction of patients on long-term administration of digoxin

Various data suggest that male patients who have received digoxin on a longterm basis have increased levels of serum estrogen and decreased levels of plasma testosterone and luteinizing hormone (LH). This study was undertaken to investigate the links between the long-term administration of digoxin therapy and sexual behavior, and the effect of digoxin on plasma levels of estradiol, testosterone, and LH. The patients of the study and control group (without digoxin) were of similar cardiac functional capacity and age (25–40 years) and were randomly selected from the rheumatic heart disease patients. A subjective assessment of sexual behavior in the study and control groups was carried out, using parameters such as sexual desire, sexual excitement, and frequency of sexual relations. Personal interviews and a questionnaire were also used for the evaluation of sexual behavior. The findings support the reports concerning digoxin effect on plasma estradiol, testosterone, and LH. The differences in the means were significant. Tests used to evaluate the changes in sexual behavior showed a significant decrease in sexual desire, sexual excitement phase (erection), and frequency of sexual relations in the study group.     

Sex hormones and adrenocortical steroids in men acutely intoxicated with ethanol

The plasma or serum concentrations of testosterone, LH, FSH, PRL, cortisol, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, estrone and estradiol were monitored in 8 healthy male volunteers for a period of 48 hr after administration of one large dose of ethanol (1.75 g/kg BW) within the first 3 hr of the experiment. Each subject served as his own control in an identical experiment without ethanol. Blood alcohol concentration reached a maximum of 1.51±0.08g/l (mean±SEM) 4 hr after the start of drinking. The maximum decrease in serum testosterone was observed at 12 hr when the serum concentrations of gonadotropins were still unchanged. The decrease in serum testosterone persisted at 24 hr despite increases in the serum levels of LH and FSH. The serum or plasma concentrations of PRL, cortisol, 17-hydroxyprogesterone, androstenedione and dehydroepiandrosterone were clearly increased 4 hr after the start of drinking. The increase in serum cortisol lasted as long as the decrease in serum testosterone. No significant changes were found in plasma concentrations of estrone and estradiol. Our results suggest that in addition to direct testicular effects of alcohol, increased adrenal secretion of cortisol may contribute to the decrease in serum testosterone in men acutely intoxicated with ethanol.     

Use of a new drug delivery formulation of the gonadotrophin-releasing hormone analogue Deslorelin for reversible long-term contraception in male dogs

In the present study, we tested the effect of treatment with a slow-release implant containing the gonadotrophin-releasing hormone agonist Deslorelin(TM) (Peptech Animal Health Australia, North Ryde, NSW, Australia) on pituitary and testicular function in mature male dogs. Four dogs were treated with Deslorelin (6-mg implant) and four were used as controls (blank implant). In control dogs, there were no significant changes over the 12 months of the study in plasma concentrations of luteinising hormone (LH) or testosterone, or in testicular volume, semen output or semen quality. In Deslorelin-treated dogs, plasma concentrations of LH and testosterone were undetectable after 21 and 27 days, testicular volume fell to 35% of pretreatment values after 14 weeks and no ejaculates could be obtained after 6 weeks. Concentrations returned to the detectable range for testosterone after 44 weeks and for LH after 51 weeks and both were within the normal range after 52 weeks. Semen characteristics had recovered completely by 60 weeks after implantation. At this time, the testes and prostate glands were similar histologically to those of control dogs. We conclude that a single slow-release implant containing 6 mg Deslorelin has potential as a long-term, reversible antifertility agent for male dogs.     

Effect of dietary intake on steroid feedback on release of luteinizing hormone in ovariectomized cows

This study tested the hypothesis that the decline in pulsatile release of luteinizing hormone (LH), resulting from steroid negative feedback, is greater in animals fed a low, compared with a high, plane of nutrition. Two-year-old cows were ovariectomized and six days later were fed diets to provide 1.5 x maintenance requirements (n = 6, supplemented) or 0.5 x maintenance requirements (n = 6, restricted) (Round 1). Pulsatile release of LH was measured over a 14-h period on the fifth day of feeding these diets (Day 1); at 6 h, all animals were treated with an intravaginal insert containing 1.38 g progesterone, which remained in place until the end of Day 3. Pulsatile release of LH was again measured for 14 h on Day 3; at 6 h, all animals were injected intramuscularly with oestradiol benzoate (ODB; 1 mg per 500 kg live weight). Three days later, this protocol was repeated, in a cross-over design, with cows that were previously restricted now being supplemented and those cows previously supplemented, now restricted (Round 2). Plasma concentrations of progesterone after intravaginal progesterone treatment were 1.01 ng mL(-1) higher in restricted cows compared with supplemented cows (P < 0.001) and were also higher in Round 1 than in Round 2 and on Day 1 than on Day 3 (P < 0.001). Plasma concentrations of oestradiol following injection with ODB did not differ between supplemented and restricted cows (P > 0.1). Dietary intake did not affect mean concentrations of LH, pulse frequency or amplitude during the 6-h period before steroid treatment or the change in these variables following steroid treatment; however, the slope of the decline in concentrations of LH following progesterone treatment was significantly more negative in cows fed restricted diets compared with those fed supplemented diets. In Round 2, mean concentrations of LH were higher preceding, and decreased more following, progesterone treatment compared with the decrease after ODB treatment. In conclusion, acute dietary restriction resulted in a more rapid decline in the release of LH following treatment with intravaginal progesterone, and was associated with higher concentrations of progesterone in plasma.     

Endocrine Response to a Single Injection of Goserelin 3.6 mg or Leuprolide 3.75 mg in Men with Prostate Cancer

Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who were randomized to receive either a single injection of goserelin 3.6 mg or leuprolide 3.75 mg. Testosterone increased over the first week, with a significantly higher mean rate of change of total testosterone (day 3) and free testosterone (days 3 and 7) with leuprolide. Following the initial rise in luteinizing hormone (LH), the rate of decrease in LH levels was significantly greater with goserelin by day 28. There are significant differences in endocrine response to goserelin and leuprolide in the 4 weeks following administration.     

Suppressive effect of quinalphos on the activity of accessory sex glands and plasma concentrations of gonadotrophins and testosterone in rats

Biochemical estimation of prostatic acid phosphatase and fructose content in accessory sex glands, along with radioimmunoassay of plasma gonadotrophins (FSH and LH) and testosterone were performed in Wistar rats following treatment with quinalphos, an organophosphorus insecticide, for 13 and 26 days. Prostatic acid phosphatase activity and fructose content of the accessory sex glands, and plasma levels of testosterone and FSH were significantly lower in all rats treated with quinalphos. However, the degree of inhibition was more extensive in the 26 day-treatment group who, in addition also exhibited a significant reduction in relative weights of the testes and accessory sex organs, and plasma levels of LH. All these adverse effects of quinalphos were prevented when exogenous HCG was administered in concomitant with the insecticide for 26 days. These results suggest that quinalphos may exert a suppressive effect on the functional activity of accessory sex glands by decreasing testicular testosterone production following inhibition of pituitary gonadotrophins release.     

Effects of benzo(a)pyrene on intra-testicular function in F-344 rats

The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 (F-344) rats to inhaled benzo(a)pyrene (BaP), a ubiquitous environmental toxicant present in cigarette smoke, automobile exhaust fumes and industrial emissions. Rats were assigned randomly to a treatment or control group. Treatment consisted of exposure of rats via nose-only inhalation to 75 microg BaP/m3, 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately on day 60 of exposures (time 0) and subsequently at 24, 48, and 72 hours, to assess the effect of exposures to BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Mean testis weight, total weight of tubules and total tubular length per paired testes were reduced 33% (P < 0.025), 27% (P < 0.01) and 39%, respectively in exposed rats (P < 0.01) compared with UNC rats. The number of homogenization -resistant spermatids was significantly reduced in BaP-exposed versus UNC rats. Plasma testosterone and intra-testicular testosterone (ITT) concentrations were significantly decreased by BaP compared with those of UNC rats. The decreases in circulating plasma testosterone were accompanied by concomitant increases in plasma LH concentrations in BaP-exposed versus control rats (P < 0.05). These data suggest that 60 days exposure to inhaled BaP contribute to reduced testicular endocrine and spermatogenic functions in exposed rats.