Unexpected Role of α-Fetoprotein in Spermatogenesis

BACKGROUND: Heat shock severely affects sperm production (spermatogenesis) and results in a rapid loss of haploid germ cells, or in other words, sperm formation (spermiogenesis) is inhibited. However, the mechanisms behind the effects of heat shock on spermatogenesis are obscure. METHODOLOGY/PRINCIPAL FINDINGS: To identify the inhibitory factor of spermiogenesis, experimental cryptorchid (EC) mice were used in this study. Here we show that α-fetoprotein (AFP) is specifically expressed in the testes of EC mice by proteome analysis. AFP was also specifically localized spermatocytes by immunohistochemical analysis and was secreted into the circulation system of EC mice by immunoblot analysis. Since spermatogenesis of an advanced mammal cannot be reproduced with in vitro, we performed the microinjection of AFP into the seminiferous tubules of normal mice to determine whether AFP inhibits spermiogenesis in vivo. AFP was directly responsible for the block in spermiogenesis of normal mice. To investigate whether AFP inhibits cell differentiation in other models, using EC mice we performed a partial hepatectomy (PH) that triggers a rapid regenerative response in the remnant liver tissue. We also found that liver regeneration is inhibited in EC mice with PH. The result suggests that AFP released into the blood of EC mice regulates liver regeneration by inhibiting the cell division of hepatocytes. CONCLUSIONS/SIGNIFICANCE: AFP is a well-known cancer-specific marker, but AFP has no known function in healthy human beings. Our findings indicate that AFP expressed under EC conditions plays a role as a regulatory factor in spermatogenesis and in hepatic generation

Supplementary Material for: Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion

<b><i>Background/Aims:</i></b> Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency. <b><i>Methods:</i></b> A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH⁶⁷) given as one (GH^67×1; n = 35) or two daily injections (GH^33×2; n = 36), or to remain on a single 33 µg/kg/day dose (GH^33×1; n = 40). Growth was assessed as height_SDSgain for prepubertal, pubertal and total periods, as well as AH_SDS versus the population and the midparental height. <b><i>Results:</i></b> Pubertal height_SDSgain was greater for patients receiving a high dose (GH⁶⁷, 0.73) than a low dose (GH^33×1, 0.41, p < 0.05). AH_SDS was greater on GH⁶⁷ (GH^67×1, -0.84; GH^33×2, -0.83) than GH³³ (-1.25, p < 0.05), and height_SDSgain was greater on GH⁶⁷ than GH³³ (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height_SDS. <b><i>Conclusion: </i></b>Pubertal height_SDSgain and AH_SDS were dose dependent, with greater growth being observed for the GH⁶⁷ than the GH³³ randomization group; however, there were no differences between the once- and twice-daily GH⁶⁷ regimens

Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.

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Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosages were: GH, 0.1 IU/kg · day; oxandrolone, 0.05 mg/kg · day; and ethinyl estradiol, 100 ng/kg · day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.published_or_final_versio