Spermatic and peripheral oestradiol levels in patients affected by azoospermia due to seminiferous tubular damage

Taguchi

Hirano

et al. 2003

ABSTRACT. Two azoospermic dogs with high plasma estradiol-17β (E 2 ) levels were subcutaneously injected with an aromatase inhibitor (AI), 4-androstene-4-ol-3,17-dione, 2 mg every other day for 4 weeks. Before the AI treatment the plasma E 2 levels of the two dogs (21 and 22 pg/ml, respectively) were higher than those of 2 normal dogs (8.1 and 12.3 pg/ml), and they fell to 11-17 pg/ml between 1 and 4 weeks after the start of AI treatment. The plasma testosterone levels after the start of AI treatment had increased to 2.1-3.1 ng/ ml. A small number of sperm were detected in the semen of the two dogs between 3 and 6 weeks after the start of AI treatment. Th ese results indicate that the testicular function of infertile dogs with high plasma E 2 levels can be temporarily improved by AI therapy. KEY WORDS: aromatase inhibitor, azoospermia, canine.J. Vet. Med. Sci. 65(12): 1343-1345, 2003 A portion of the testosterone (T) produced by the testis is converted to estradiol-17β (E 2 ) by aromatase enzyme activity [11]. In the testes of many species [2,17], including dogs [3], the E 2 -secreting cells are the Sertoli cells and/or the Leydig cells [13,20]. In men [6,19] abnormally increased testicular E 2 production causes spermatogenic dysfunction, and long-term E 2 administration has been shown to inhibit spermatogenesis in dogs [8,15]. Aromatase inhibitor (AI) blocks the aromatization of androgen to E 2 by inhibiting aromatase enzyme activity [1,18], and AI has been reported to be effective in treating spermatogenic dysfunction in men with high plasma E 2 levels [4]. In the present study, two azoospermic dogs with abnormally increased plasma E 2 levels were treated with AI to improve poor semen quality. Plasma E 2 levels after administration of follicle stimulating hormone extracted from porcine pituitary gland (FSH-P) were measured to investigate the main E 2 -secretory cells in canine testes.The two azoospermic dogs used to assess the effects of AI treatment were a Miniature Poodle (Dog 1) and a Beagle (Dog 2), aged 5 and 2 years, respectively. Dog 1 was owned by a breeder, and Dog 2 was cared for in our university. None of a few bitches mated with either of the two male dogs had conceived. Four semen specimens were collected by digital manipulation with a teaser bitch at one-week intervals. Each specimen was examine for total semen volume, total number of sperm, and morphologically abnormal sperm by the methods described previously [9]. As no sperm had been found in the semen of either Dog 1 or Dog 2 (Table 1), both of them were diagnosed as having azoospermia. Although the two azoospermic dogs were treated with 3 intramuscular injections of 1000 IU hCG per head at one-week intervals, their semen quality had failed to improve. Peripheral blood samples were collected from the two azoospermic dogs at the same time as the semen collections. Plasma E 2 and T levels were measured by the radioimmunoassay described previously [8]. The plasma E 2 levels of the two dogs (21 and 22 pg/ml, respectively) were higher than those o...

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Therapeutic Effect of Aromatase Inhibitor in Two Azoospermic Dogs with High Plasma Estradiol-17β Levels

Taguchi

Hirano

et al. 2003

“…Infertility in a few human patients has been attributed to elevated testicular E 2 concentrations [13], and the plasma E 2 levels of some azoospermic men have been found to be higher than those of normal men [9,29]. Long term E 2 administration has been shown to inhibit T secretion by the testis in rats [28], to cause the disappearance of spermatids and spermatozoa from the seminiferous tubules of bull testes [21], and to induce the testicular atrophy of dogs [15].…”

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confidence: 99%

High Plasma Estradiol-17.BETA. Levels in Dogs with Benign Prostatic Hyperplasia and Azoospermia.

Amemiya

Namikawa

et al. 2001

ABSTRACT. The semen quality of 22 dogs (4 to 7 years old) with benign prostatic hyperplasia (BPH) was examined at the hospital of our university, and 4 of the 22 BPH dogs were diagnosed as azoospermic. The mean peripheral plasma estradiol-17β (E 2 ) level (17.3 pg/ ml) of the 18 BPH dogs with spermatogenic function was higher than that of 5 normal male dogs and their mean T level (1.7 ng/ml) was lower. The mean E 2 level (27.3 pg/ml) of the 4 BPH dogs with azoospermia was significantly higher than the value in the BPH dogs with spermatogenic function (P<0.01), and the mean T level (1.1 ng/ml) was significantly lower (P<0.05). Five normal male dogs were given 10 intramuscular injections of estradiol benzoate (E 2 B) 5 µg/kg, at 3-day intervals to investigate the relationship between high plasma E 2 levels and the cause of the BPH and azoospermia. Their testes and prostates were measured and biopsied both before and 30 days after the start of E 2 B injections. At 30 days after the start of the E 2 B injections, the mean peripheral plasma T levels had decreased by half, and the mean testicular volume had decreased to 88% of original volume. The numbers of spermatocytes, spermatids, and spermatozoa in the seminiferous tubules of all of the dogs were significantly lower (P<0.05, 0.01). In addition, the mean prostatic volume increased to 130%, the mean height of the glandular epithelium decreased, and the glandular lumen became increased in diameter. These findings indicate that both BPH and serious spermatogenic dysfunction may be simultaneously induced by protracted high plasma E 2 levels in dogs. KEY WORDS: azoospermia, benign prostatic hyperplasia, canine, estradiol-17β.J. Vet. Med. Sci. 63(4): 407-412, 2001 Canine benign prostatic hyperplasia (BPH) in dogs is known to occur chiefly in animals more than 6 years old [6], and its occurrence is presumed to be associated with abnormal estradiol-17β (E 2 ) and testosterone (T) secretion by the testes associated with advanced age [5,19]. T is converted to 5α-dihydrotestosterone (DHT) in the canine prostate, and prostatic function is maintained by the androgen effects of DHT [10,11]. DHT concentration in the prostates of dogs with BPH has been reported to be higher than in normal dogs [8,14]. Accumulation of DHT in the prostate is accelerated by high plasma E 2 levels and is thought to cause BPH [8,14].Testicular and plasma E 2 are produced by both Leydig cells and Sertoli cells [23]. Infertility in a few human patients has been attributed to elevated testicular E 2 concentrations [13], and the plasma E 2 levels of some azoospermic men have been found to be higher than those of normal men [9,29]. Long term E 2 administration has been shown to inhibit T secretion by the testis in rats [28], to cause the disappearance of spermatids and spermatozoa from the seminiferous tubules of bull testes [21], and to induce the testicular atrophy of dogs [15]. However, in many cases the cause of spermatogenic arrest in dogs is unknown [7,24]. In the present study, the peripheral pla...

“…The high concentrations of testicular Tf in the AZ dogs in the present study are assumed to reflect the high plasma E 2 concentrations caused by excessive E 2 production by Sertoli cells. Leydig cells and spermatogenic dysfunction have been found to be induced by E 2 administration [7,15], and high testicular E 2 concentrations have been reported to be a cause of infertility in humans [4]. Although the causes in many cases of spermatogenic arrest in the dog are unknown [3,14], some cases of azoospermia caused by low testosterone secretory function of Leydig cells and inhibition of spermatogenesis in the dog have been demonstrated to be the result of excessive E 2 secretion by Sertoli cells.…”

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“…However, Sertoli cell tumors in the dog sometimes cause feminization of behavior, alopecia, pigmentation, nipple enlargement, and atrophy of the unaffected testis [9,10]. It has been reported that high E 2 output by the testes causes azoospermia in humans [4,17]. Transferrin (Tf), a glycoprotein secreted by Sertoli cells, transports Fe ions to germ cells [6,16], and testicular Tf concentrations are useful as an index of Sertoli cell function [13].…”

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Relationship between Testicular Transferrin and Plasma Estradiol-17.BETA. Concentrations of Dogs with Azoospermia and Dogs with Sertoli Cell Tumors.

Hori

Tsutsui

2001

ABSTRACT. Testicular Transferrin (Tf) and peripheral plasma estradiol-17β (E 2 ) concentrations were measured in 3 dogs with azoospermia (AZ dogs), 3 dogs with Sertoli cell tumors (SC dogs), and 5 normal male Beagles. The mean Tf concentrations in the testes of the AZ dogs and the affected testes of the SC dogs, and the plasma E 2 concentrations in both these groups of dogs were significantly higher than the values in normal dogs (P<0.05, 0.01 and 0.01, respectively). Therefore, excessive E 2 secretion by hyperfunctioning Sertoli cells is thought to have caused the azoospermia in the 3 dogs.