Chronic human chorionic gonadotropin administration in normal men: evidence that follicle-stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man

The role of FSH in the maintenance of spermatogenesis in man is poorly understood. To determine whether normal serum levels of FSH are necessary for the maintenance of quantitatively normal spermatogenesis, we first studied the effect on sperm production of selective FSH deficiency induced by chronic administration of hCG in normal men. Then, we determined the effect of FSH replacement in some of these men. After a 3-month control period, eight normal men (aged 30-39 yr) received 5000 IU hCG, im, twice weekly for 7 months. Then while continuing the same dosage of hCG, subjects simultaneously received 200 mg testosterone enanthate (T), im, weekly for an additional 6 months. hCG administration alone resulted in partial suppression of the mean sperm concentration from 88 +/- 24 (+/-SEM) million/ml during the control period to 22 +/- 7 million/ml during the last 4 months of hCG treatment (P less than 0.001 compared to control values). With the addition of T to hCG, sperm counts remained suppressed to the same degree. Except for one man who became azoospermic while receiving hCG plus T, sperm motilities and morphologies remained normal in all subjects throughout the entire study. During both the hCG alone and hCG plus T periods, serum FSH levels were undetectable (less than 25 ng/ml), and urinary FSH levels were comparable to those in prepubertal children and hypogonadotropic hypogonadal adults. We replaced FSH activity in four of the eight men in whom prolonged selective FSH deficiency and partial suppression of sperm production were induced by hCG administration. Immediately after the period of hCG plus T administration, T was stopped in four men who continued to receive hCG alone (5000 IU, im, twice weekly) for 3 months. Then, while continuing the same dosage of hCG, these men received 100 IU human FSH, sc, daily (n = 2) or 75 IU human menopausal gonadotropin, sc, daily (n = 2) for 5-8 months. During the second period of hCG administration alone, serum FSH levels were undetectable (less than 25 ng/ml), and sperm concentrations were suppressed (34 +/- 13 million/ml) compared to the control values for these four men (125 +/- 39 million/ml; P less than 0.001). With the addition of FSH to hCG, FSH levels increased (213 +/- 72 ng/ml) and sperm concentrations rose significantly, reaching a mean of 103 +/- 30 million/ml (P less than 0.03 compared to hCG alone).(ABSTRACT TRUNCATED AT 400 WORDS

Elevated serum follicle-stimulating hormone levels in men with normal seminal fluid analyses

Three men who volunteered as normal subjects were found to have abnormally high levels of serum follicle-stimulating hormone (FSH) despite having normal seminal fluid analyses and fertility. Two of the men had a history of previous orchitis, and one had an atrophic testis. Serum luteinizing hormone and testosterone levels were normal. These cases appear to represent compensated primary testicular disease, with normal sperm counts and fertility maintained at the expense of chronically elevated FSH levels. These results imply that in certain situations, the measurement of serum FSH levels may be a more sensitive index of testicular disease than the performance of seminal fluid analyses

Diminished luteinizing hormone pulse frequency and amplitude with aging in the male rat

Aging in the male rat is associated with a reduction in circulating testosterone levels. One possible cause of this decline is an age-related alteration of central nervous system-mediated LH secretion. To examine the effects of age on the hypothalamo-hypophyseal system, in the absence of gonadal steroid feedback, we studied the pattern of pulsatile LH secretion in castrate male Sprague-Dawley rats, aged 3 months (young), 8 months (middle-aged), and 26 months (old). All animals were castrated, and after 3 weeks, they were implanted with indwelling atrial catheters. One day later, duplicate 25 microliters blood samples were obtained at 4-min intervals for 4 h, while the animals were awake and unrestrained. Serum levels of LH, FSH, and testosterone were measured in animals before castration, and blood LH levels were measured in the postcastration, repeated sampling studies. After castration, middle-aged and old animals exhibited significantly lower mean serum LH levels, associated with a diminished amplitude of LH secretory episodes compared to young rats. In the oldest group, LH pulse frequency was significantly lower compared to middle-aged and young animals. Since the control of LH secretory episodes resides in the central nervous system, we propose that alterations in frequency of LH pulses observed in the aged, castrate male rat are the result of a diminished functional capacity of LHRH-containing neurons or of neurotransmitters that modulate their activity in the aging brain

Evidence for activation of the central nervous system-pituitary mechanism for gonadotropin secretion at the time of puberty in the male rat

During sexual development in the male rat, serum testosterone (T) levels increase markedly at 45-60 days of age. At the time of the pubertal rise in T levels, activation of the hypothalamic-pituitary axis is difficult to demonstrate, since there is little change in serum LH levels and a decrease in serum FSH levels. We determined whether experimental maintenance of stable pubertal T levels in these animals as they passed through the normal age of puberty would allow demonstration of a major increase in serum gonadotropin levels. At 14-15 days of age, male rats were castrated and outfitted with either T-containing or empty Silastic capsules. Another group of rats was left intact and outfitted with empty capsules. At various times between 29 and 58 days of age, blood was drawn for measurement of serum LH, FSH, and T levels. In the T-implanted castrated rats, serum T levels were comparable to those in midpubertal intact rats, without significant differences among age groups. In this setting of stable T levels, serum LH and FSH were suppressed to levels at or below those in pubertal intact rats until 51 days of age, when they increased significantly into the untreated castrate range. In contrast, untreated castrate animals demonstrated markedly reduced serum T and elevated LH and FSH levels that did not change significantly throughout the entire study. In intact rats, serum T levels were stable until 58 days of age, when they increased over 2-fold; serum LH levels did not change significantly with age, and serum FSH levels decreased significantly by 54 days of age. A separate group of rats was castrated and outfitted with T-containing Silastic capsules at 21 days of age. In these animals, there were significant increases in hypothalamic LHRH, norepinephrine (NE), and dopamine levels and NE turnover rate at 56 compared to 36 days of age. We conclude that stable pubertal levels of T are able to suppress gonadotropin levels in castrated rats until the normal age of puberty, at which time LH and FSH levels increase markedly. This decrease in sensitivity of the hypothalamic-pituitary axis to T negative feedback at puberty is accompanied by increases in hypothalamic LHRH, NE, and dopamine levels and NE turnover rate. These results provide direct evidence for activation of the central nervous system-pituitary mechanism regulating gonadotropin secretion at puberty in the male rat.(ABSTRACT TRUNCATED AT 400 WORDS