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PubMed1990

An enzyme linked immunoassay for anti-müllerian hormone: a new tool for the evaluation of testicular function in infants and children.

Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance or factor was measured by an interspecific enzyme-linked immunoassay in the serum of 218 normal children and adults of both sexes and in 110 boys with various developmental disorders. AMH levels were high [81.67 ng/ml +/- 7.44(SEM)] in normal males under 2 yr of age, fell progressively in older boys and, decreased sharply at puberty. Serum AMH was not detectable in adults or in females at any age, with very rare exceptions. AMH serum concentrations were significantly decreased in infants with disorders of sex differentiation, particularly testicular dysgenesis, and increased in patients with delayed puberty. In contrast, levels were not significantly affected by either cryptorchidism or chorionic gonadotropin stimulation. AMH shows promise as a marker of testicular function in infancy.

Adolescent↗
PubMed1996

Androgen regulation of growth hormone binding protein.

Male puberty is associated with elevated plasma concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I), as well as accelerated linear growth. These effects can be reproduced by administration of testosterone (T). To further elucidate the mechanisms underlying pubertal growth, we treated 14 boys with delayed puberty and short stature with either T (n = 7) or 5alpha-dihydrotestosterone (DHT) (n = 7) and compared the effect on plasma concentrations of GH, IGF-I, and GH binding protein (GHBP). Before treatment and after either three or four doses of T enanthate or DHT heptanoate, mean 12-hour GH concentration (8 AM to 8 PM) and plasma IGF-I, T, DHT, and GHBP levels were measured, and height velocity (HV) was measured over this interval. T treatment resulted in an increase of mean GH from 3.3 to 12.0 microg/L (P < .005) and of IGF-I from 22.3 to 45.4 nmol/L (P < .01). During treatment, HV was 11.0 +/- 1.1 cm/yr, consistent with normal pubertal growth, and plasma T was 22.5 +/- 5.3 nmol/L. GHBP decreased in this group from 937 to 521 pmol/L (P < .025). DHT treatment resulted in a small decrease of mean GH from 4.3 to 2.9 microg/L (P < .025) and of IGF-I from 29.4 to 27.2 nmol/L (nonsignificant [NS]). During treatment, HV was 9.3 +/- 1.1, not significantly different from the HV obtained with T treatment, and plasma DHT was 24.2 nmol/L at 1 week and 29.2 at 2 weeks postinjection. Likewise, there was a decrease in GHBP from 928 to 698 pmol/L (P < .025). The decline in GHBP with T treatment was apparently due to an androgen receptor-dependent mechanism, since the same effect was seen during treatment with the nonaromatizable androgen, DHT. This effect is opposite to the normal chronological trend upward for GHBP, which occurs from infancy into midpuberty. Factors determining the upward trend are not known, but are evidently independent of the plasma concentration of sex hormones and GH. The increase in IGF-I in response to T treatment despite a moderate decline in GHBP (and possibly GH receptor) levels is most likely due to the large increase in GH, which may override a modest decrease in GHBP/GH receptor.

Adolescent↗
PubMed1986

[Puberty induction using pulsatile LHRH administration].

Puberty is a maturational process of the hypothalamo-pituitary-gonadal axis resulting in growth and development of the genital organs and concomitantly physical changes. All these changes are the result of an increasing activity of the pituitary and consequently of the gonads caused by increased stimulation by the luteinizing hormone-releasing hormone (LHRH). Delayed puberty is a common problem in contrast to true hypogonadotropic hypogonadism. Since a few years pulsatile LHRH administration is applied to induce pubertal development in hypogonadotropic boys. Except for virilisation, development of the testes including spermatogenesis can be achieved. In contrast to boys, substitution with sex steroids brings about a satisfactory physiologic development of the sex characteristics in girls. The physiology and disorders of pubertal development as well as this new LHRH treatment to induce puberty will be discussed in this paper.

Child↗
PubMed1979

Melatonin, the pineal gland and human puberty.

Animal experiments have suggested that the pineal gland produces an anti-gonadotropic hormone. The hamster, for example, undergoes reproductive collapse when kept in short-day periods, an effect which is abolished by pinealectomy. Although there is little direct evidence about the endocrine role of the pineal gland in man, it has been noted that tumours of the pineal gland in young boys are associated with precocious puberty and the human pineal gland has been suggested to produce a substance that holds sexual maturation in check. This observation has been extended by Kitay, who has shown that destructive tumours are associated with precocious puberty whereas hyperactive tumours are associated with delayed puberty. However, no studies have described any change of pineal function with normal puberty. Because two pineal indoles, melatonin and methoxytryptophol, have been shown to be antigonadotropic when administered to animals, we have now measured them in schoolchildren. Our findings show that in young boys there is an abrupt fall in the concentration of melatonin with advancing development suggesting that it may play an important physiological role in the control of human puberty.

Adolescent↗
PubMed1997

Estrogen and testosterone, but not a nonaromatizable androgen, direct network integration of the hypothalamo-somatotrope (growth hormone)-insulin-like growth factor I axis in the human: evidence from pubertal pathophysiology and sex-steroid hormone replacement.

Activation of the gonadotropic and somatotropic axes in puberty is marked by striking amplification of pulsatile neurohormone secretion. In addition, each axis, as a whole, constitutes a regulated network whose feedback relationships are likely to manifest important changes at the time of puberty. Here, we use the regularity statistic, approximate entropy (ApEn), to assess feedback activity within the somatotropic (hypothalamo-pituitary/GH-insulin-like growth factor I) axis indirectly. To this end, we studied pubertal boys and prepubertal girls or boys with sex-steroid hormone deficiency treated short-term with estrogen, testosterone, or a nonaromatizable androgen in a total of 3 paradigms. First, our cross-sectional analysis of 53 boys at various stages of puberty or young adulthood revealed that mean ApEn, taken as a measure of feedback complexity, of 24-h serum GH concentration profiles is maximal in pre- and mid-late puberty, followed by a significant decline in postpubertal adolescence and young adulthood (P = 0.0008 by ANOVA). This indicates that marked disorderliness of the GH release process occurs in mid-late puberty at or near the time of peak growth velocity, with a return to maximal orderliness thereafter at reproductive maturity. Second, oral administration of ethinyl estradiol for 5 weeks to 7 prepubertal girls with Turner's syndrome also augmented ApEn significantly (P = 0.018), thus showing that estrogen per se can induce greater irregularity of GH secretion. Third, in 5 boys with constitutionally delayed puberty, im testosterone administration also significantly increased ApEn of 24-h GH time series (P = 0.0045). In counterpoint, 5 alpha-dihydrotestosterone, a nonaromatizable androgen, failed to produce a significant ApEn increase (P > 0.43). We conclude from these three distinct experimental contexts that aromatization of testosterone to estrogen in boys, or estrogen itself in girls, is likely the proximate sex-steroid stimulus amplifying secretory activity of the GH axis in puberty. In addition, based on inferences derived from mathematical models that mechanistically link increased disorderliness (higher ApEn) to network changes, we suggest that sex-steroid hormones in normal puberty modulate feedback within, and hence network function of, the hypothalamo-pituitary/GH-insulin-like growth factor I axis.

Adolescent↗
PubMed2000

Biliary atresia with hyperandrogenic amenorrhea: case report.

The etiology of hyperandrogenic amenorrhea in a 16 year-old girl after a successful Kasai operation for biliary atresia was unclear. Delayed puberty and menarche were observed. There was no luteinizing hormone-follicular stimulating hormone surge. A provocative luteinizing hormone-releasing hormone test showed a normal response. Peripheral aromatization of androgens appeared to function normally. However, plasma levels of sex hormone-binding globulin and total testosterone were high and the free testosterone level was normal. The anovulatory menstrual cycle continued after menarche at 18 years of age. A combination of estrogen and progesterone therapy was effective. The etiology might be associated with delayed metabolic clearance of testosterone accompanied by the compensatory cirrhosis and portosystemic shunt.

Adolescent↗
PubMedDate not supplied

The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats.

This study was designed to determine if long-term exposure to high doses of methoxychlor (M) would alter pituitary or testicular endocrine functions in either an estrogenic or antiandrogenic manner. Weanling male Long-Evans hooded rats were dosed daily with M (po) at 0, 200, 300, or 400 mg kg-1 day-1 for 10 months. Methoxychlor treatment delayed puberty by as much as 10 weeks and reduced fertility and copulatory plug formation in a dose-related manner at the initial mating. During mating, M-treated males exhibited shorter latencies to mount and ejaculate versus control males, but the number of intromissions prior to ejaculation was unaffected, indicating that M enhanced the arousal level in the males in an estrogen-dependent manner. Most treated males eventually mated but time-to-pregnancy was lengthened. Very low sperm counts were associated with infertility, while prolonged delays in puberty reduced fecundity. Methoxychlor treatment with 200 to 400 mg kg-1 day-1 failed to mimic the chronic effects of a sustained (8 months) low dose of estradiol-17 beta (3-mm silastic implants) on pituitary or testicular hormone levels. Estradiol administration increased pituitary weight 4-fold, serum levels of luteinizing hormone (LH) were reduced by almost 50%, and serum prolactin was increased 40-fold, while M did not affect any of these measures. These data demonstrate that M affects the CNS, epididymal sperm numbers, and the accessory sex glands and delays mating without significantly affecting the secretion of LH, prolactin, or testosterone. These data indicate that M did not alter pituitary endocrine function in either an estrogenic or antiandrogenic manner. To our knowledge, these data provide the first in vivo example of such a pronounced degree of target tissue selectivity to an environmental endocrine-disrupting chemical.

Animals↗
PubMed1985

[The delay of bone maturation is a favorable element in the prognosis of final height].

Final heights were studied in 54 children followed for several years for growth retardation with delayed puberty. At the time of the first visit (13 9/12 in boys, 11 10/12 +/- 13/12 in girls), growth retardation was -2.7 +/- 0.8 in boys and -2.8 +/- 0.8 SD in girls. Retardation of bone age with respect to chronological age was always significant (2 7/12 +/- 10/12 yrs in boys and 2 7/12 +/- 9/12 in girls). Catch-up, calculated in terms of standard deviation score (SDS) between the first visit score and the final height was established for each child, as was the prognosis of height according to 3 methods (Bayley, Tanner, Roche). There is a highly significant correlation (r = 0.49; p less than 0.001) between the ratio of delayed bone age/chronological age (BA/CA) and the height catch-up calculated in SDS. On the contrary there is no correlation between the ratio BA/CA and the final height. This lack of correlation may be explained by the role taken by others factors, especially the parents heights, as a significant correlation was found between the final heights, the fathers heights (r = 0.29) and the mothers heights (r = 0.36). Thus, delayed bone maturation may be considered as a favourable factor for the prognosis of adult height.

Adolescent↗
PubMed2005

In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture.

PBDEs have been synthesized in large quantities as flame retardants for commercial products, such as electronic equipment and textiles. The rising in levels of PBDEs in tissues in wildlife species and in human milk and plasma samples over the past several years have raised concerns about possible health effects. Recently, we showed that the PBDE mixture, DE-71, delayed puberty and suppressed the growth of androgen-dependent tissues in male Wistar rat following a peri-pubertal exposure. These effects suggested that DE-71 may be either inducing steroid hormone metabolism or acting as an androgen receptor (AR) antagonist. To elucidate the potential anti-androgenic effects of this mixture, we evaluated DE-71 in several in vivo assays, which are responsive to alterations in androgen activity. In a pubertal exposure study designed to further evaluate the delay in preputial separation (PPS), we observed a dose-dependent delay in PPS with 60 and 120 mg/kg/day of DE-71 (4 and 5 days) and a corresponding suppression of ventral prostate (VP) and seminal vesicle growth at both doses. Adult males exposed to 60 mg/kg DE-71 for 3 days resulted in a significant increase in luteinizing hormone and a non-significant increase in testosterone, androstenedione and estrone. DE-71 also tested positive for anti-androgenic activity in an immature rat Hershberger assay, with decreases in mean VP and seminal vesicle weight following doses of 30-240 mg/kg. DE-71 and the individual BDE congeners which comprise the mixture (BDE-47, -99, -100, -153, -154) were also evaluated in vitro. First, AR binding was evaluated in a competitive binding assay using rat VP cytosol. In addition, we evaluated gene activation in a transcriptional activation assay using the MDA-kb2 cell line which contains an endogenous human AR and a transfected luciferase reporter. DE-71 and BDE-100 (2, 4, 6-pentaBDE) both inhibited AR binding, with IC50s of approximately 5 microM. In addition, DE-71 and two of the congeners (BDE-100 and BDE-47) inhibited DHT-induced transcriptional activation. The pattern of inhibition shown in the double-reciprocal plot for BDE-100 and the linear slope replot confirmed that the in vitro mechanism is pure competitive inhibition, with a inhibition constant (Ki) of 1 microM. The delay in puberty in the male rat and decreased growth of androgen-dependent tissues observed previously following exposure to DE-71 were likely due to this inhibition of AR binding by several of the congeners which make up this mixture.

Androgen Antagonists↗
PubMed2005

The adult phenotype in Costello syndrome.

We report clinical findings in 17 adults with Costello syndrome ranging in age from 16 to 40 years. Two patients in this series have had bladder carcinoma, the only malignancy reported to affect adults with Costello syndrome. Benign tumors included multiple ductal papillomata in two women, and a fourth ventricle mass in one man, thought to be a choroid plexus papilloma. Endocrine problems in this series were osteoporosis, central hypogonadism, and delayed puberty. Other health problems were symptomatic Chiari malformations in three patients. Four patients had adult-onset gastro-esophageal reflux, three of whom had Chiari malformations. Fourteen adults had mild to moderate intellectual disability with three individuals having severe intellectual disability; 15 individuals attained some reading and writing skills and 14 showed ongoing acquisition of new skills into adulthood. On the basis of this data, we recommend that neuro-imaging be considered in adults with Costello syndrome if they develop symptoms suggestive of a Chiari malformation. In the event of pubertal delay, endocrine investigations are indicated and hormone treatment may be required. Bone density assessments should be performed in adults with Costello syndrome, particularly in those with pubertal abnormalities. Screening for microscopic hematuria as a marker for bladder carcinoma may be indicated, although this requires further evaluation.

Abnormalities, Multiple↗
PubMed2006

Lack of puberty despite elevated estradiol in a 46,XY phenotypic female with Frasier syndrome.

Frasier syndrome is characterized by slowly progressive nephropathy, male pseudohermaphroditism, streak gonad, and high risk of gonadoblastoma development. Here we report a case of a 46,XY phenotypic female with Frasier syndrome, who was under hemodialysis. While her serum estradiol level was gradually increasing annually, gonadotropin level was constantly extremely high, and her appearance was still prepubertal. She was heterozygous for a novel guanine>adenine point mutation at position +1 of the splice donor site within intron 9 (IVS 9 + 1G>A) of the Wilms' tumor 1 gene. The possibility of this disease should be taken into consideration whenever we encounter a patient with steroid-resistant nephrotic syndrome and delayed puberty.

Adolescent↗
PubMed1994

Long-term effects on reproductive parameters in female rats after translactational exposure to PCBs.

In an integrated series of experiments, we assessed effects of translactational exposure to Aroclor 1254 at three different ages: as young adults (2-4.5 months), as mature adults (5-8 months), and as older adults (8.5-13 months). Developing female rats were exposed postnatally to polychlorinated biphenyls (PCBs) via oral treatment of the dams on Days 1, 3, 5, 7, and 9 of lactation at the following doses: 8 micrograms/g (PCBI), 32 micrograms/g (PCBII), and 64 micrograms/g (PCBIII) in peanut oil. Normal controls (CI) and underfed nutritional controls (CII) received peanut oil. Puberty, both vaginal opening and first estrus, was delayed in PCBII and PCBIII offspring. PCB exposure at all doses had a pronounced and consistent effect on uterine response. In mature PCBII and PCBIII adults, uterine wet weights were reduced at all stages of the estrous cycle and in light-induced persistent vaginal estrus (PVE). PCBI offspring exhibited a decreased uterine weight in proestrus and in light-induced PVE. Exogenous estradiol-17 beta (0.2 microgram) given to ovariectomized offspring was less effective in causing a uterotrophic and vaginal response in all PCB-exposed offspring. Analysis of estrous cycles for 40 days at all ages indicated increases in diestrus. Fertility in young adults and mature adults was affected, with PCBIII young adults exhibiting less success with preimplantation stages, and PCBII and PCBIII mature adults showing an effect at pre- and/or postimplantation stages. As determined by patterns in estrous cycling and rate of development of PVE in 64 days of constant light, exposure to PCBs did not hasten reproductive aging at any of the ages examined. Instead, PCBIII young adults and PCBII and PCBIII older adults exhibited a delay in onset of light-induced PVE. This study demonstrates that translational exposure to a PCB mixture that has little notable effect on the dams, not only delays puberty in the female offspring, but also several months later results in decreased uterine response, impairment of fertility, and irregular cycle patterns. Reproductive aging, however, is not hastened, and even may be delayed. Many of these effects could be explained, in part, by interference with estrogen.

Animals↗
PubMed2002

Delay of growth and development in children with bronchial asthma, atopic dermatitis and allergic rhinitis.

The elevated incidence of short stature (body height < (-)x - 2s), skeletal retardation and delayed puberty in children with bronchial asthma or atopic dermatitis is generally attributed to the severity of the disorder. However, a series of findings indicate a causal influence of the atopy and the existence of atopic skeletal retardation per se.The observation that children with atopic disorders, whether bronchial asthma, atopic dermatitis or allergic rhinitis, exhibit a rate of short stature that is twice to five times higher than normal indicates atopic and thus genetically determined influences. The elevated prevalence of short stature associated with allergic rhinitis is especially significant, as this disorder cannot be included among the severe chronic disorders. The fact that skeletal retardation is more prevalent in boys than in girls by a ratio of about 2:1 and that a significantly more marked retardation of bone maturation is found in atopic in comparisons with non-atopic asthmatics also lend support to this postulation. The clinical relevance of atopic growth retardation is also supported by the close interaction of pathophysiological basal mechanisms of bone metabolism and the atopy status. Thus the local growth factor prostaglandin E(2) (PGE(2)), which is important for bone metabolism, is also a messenger substance for the immediate and late allergic reaction. The platelet-activating factor (PAF), as one of the strongest mediators in the pathogenesis of allergic disorders, influences the PGE(2) synthesis in the osteoblasts. These relationships show that atopy-dependent imbalances in the complex system of local and systemic growth factors can certainly lead to disturbance of skeletal maturation which may delay growth and development in atopic children. In order to verify these assumptions it is necessary to research the interaction of local growth factors (particularly the roles of PGE(2), PAF and IGF I) in the skeletons of children of short stature suffering from atopic disorders. This should also include the possible effects on the overall hormonal factors influencing bone maturation. Atopy should be included in the differential diagnosis programme to clarify growth and development disturbances.

Adolescent↗
PubMed1993

Isolated defect of peroxisomal beta-oxidation in a 16-year-old patient.

We describe a 16-year-old boy suffering from psychomotor retardation, sensorineuronal hearing impairment, peripheral neuropathy, hepatosplenomegaly, short stature and delayed puberty. Postnatally, muscular hypotonia, mild facial dysmorphism and delayed fontanelle closure had been noticed. At the time of our examination, adrenal cortical function was normal. Biochemical analysis revealed accumulation of very long (> C22) chain fatty acids in plasma and fibroblasts. Furthermore, elevated levels of intermediates of bile acid synthesis and phytanic acid were detectable. These findings are consistent with a defect in the peroxisomal beta-oxidation system. A generalised defect of peroxisomal function was excluded by normal plasmalogen levels in erythrocytes and normal plasmalogen de novo synthesis in fibroblasts. Immunoblotting of the peroxisomal beta-oxidation enzymes gave normal results suggesting retained immunoreactivity but catalytic inactivity of one of the enzymes involved, probably either the trifunctional protein or the peroxisomal ketothiolase. This case markedly differs clinically from the few published reports on isolated deficiencies of peroxisomal beta-oxidation. Among the patients with comparable biochemical findings, this is the first report of survival into adolescence.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1996

Luteinizing hormone, growth hormone, insulin-like growth factor-I, insulin and metabolites before puberty in heifers fed to gain at two rates.

Fall born Angus x Hereford heifers were allotted to treatments at 9 mo of age to achieve the following growth rates: 1) fed to gain 1.36 kg/d (n = 10; HGAIN); and 2) fed to gain 0.23 kg/d for 16 wk, then fed to gain 1.36 kg/d (n = 9; LHGAIN). Growth hormone (GH), insulin-like growth factor-I (IGF-I0, insulin, glucose, nonesterified fatty acids (NEFA), and progesterone were quantified in twice weekly blood samples until onset of puberty. Body weight, hip height, and pelvic area were recorded every 28 d. Frequent blood samples (n = 8 heifers/treatment) were collected every 14 d, commencing on day 29 of treatment until onset of puberty to evaluate secretion of luteinizing hormone (LH) and GH. The HGAIN heifers were younger (369 d; P < 0.001), were shorter at the hip (115 cm; P < 0.05) and had smaller pelvic area (140 cm2; P < 0.10), but body weight (321 kg) did not differ at puberty compared with LHGAIN heifers (460 d; 119 cm; 155 cm2; 347 kg, respectively). The HGAIN heifers had greater (P < 0.05) concentrations of LH, IGF-I, and insulin in serum and glucose in plasma during the first 84 d of treatment than LHGAIN heifers, whereas LHGAIN heifers had greater (P < 0.05) concentrations of GH in serum and NEFA in plasma than HGAIN heifers. On day 68 of treatment, HGAIN heifers had less mean GH (P < 0.01) and greater (P < 0.05) LH pulse frequency than LHGAIN heifers, whereas LH pulse amplitude and mean LH did not differ (P < 0.10) between treatments. Treatment did not influence secretion of LH and GH at 1 and 3 wk before puberty. Mean GH concentrations in serum and GH pulse amplitude in all heifers were greater (P < 0.05) 2 to 9 d (12.9 and 40.7 ng/ml, respectively) than 16 to 23 d (10.4 and 20.0 ng/ml, respectively) before puberty. Nutrient restriction decreased LH pulse frequency and delayed puberty in beef heifers. Furthermore, dramatic changes in mean concentration and amplitude of GH pulses just before puberty in beef heifers may have a role in pubertal development.

Animal Feed↗
PubMed2004

A case of Kallmann syndrome associated with Dandy-Walker malformation.

A 19-year-old man was admitted to our hospital for delayed puberty. At birth, he had macrocephalia and showed delayed physical and mental development. At 9 years of age, right cryptorchism was diagnosed. His parents had noticed that he could not recognize any smells since his infancy. Physical examination on admission revealed ocular hypertelorism, high myopia, high arched palate, and intermittent external strabismus. Sense of smell was scaled out by olfactometry. External genitalia were infantile. Neurological examination showed on IQ of 83, and mild truncal ataxia. Magnetic resonance imaging (MRI) showed a cystic distension of the IV ventricle, partial aplasia of the cerebellar vermis, elevation of the tentorium cerebelli, enlargement of the III ventricle, and agenesis of the corpus callosum. These findings revealed that the patient had Dandy-Walker malformation. The basal FSH, LH, and testosterone levels were all low compared with normal adult reference values. The serial LH-RH provocation tests showed stepwise LH and FSH elevation. After the fifth day of LH-RH administration, both LH and FSH responses clearly improved. Olfactory tracts were defective in MRI findings. These findings were consistent with hypogonadotropic hypogonadism of hypothalamic origin with anosmia, and the patient was therefore diagnosed with Kallmann syndrome. Sequence analysis of the KAL1 gene showed no mutation in the coding region. To our knowledge, this is the first case report of the coexistence of Kallmann syndrome and Dandy-Walker malformation in the same patient.

Adult↗
PubMedDate not supplied

Developmental effects and health aspects of soy protein isolate, casein, and whey in male and female rats.

Dietary factors other than the traditional nutrients are found in the so-called functional foods. They are becoming increasingly recognized as potentially important for maintaining good health. Soybeans are rich in such factors thought to help prevent certain chronic diseases. Soy protein isolate (SPI) is one of the three major proteins used in infant formulas sold in the United States, with casein (CAS) and whey (WPH) proteins being the others. We have been studying the health effects of these proteins. Safety concerns have developed over the consumption of soy-based infant formula, partly because of the high circulating levels of the total isoflavones (phytoestrogens) during "critical periods of infant development." There is a paucity of data on developmental, physiological, neurophysiological, behavioral, metabolic, or molecular effects of soy phytochemicals in humans, especially during pregnancy and infancy. We have studied the effects of CAS, SPI, and WPH in short-term, long-term, and multigenerational studies in rats. Aside from minor differences in body weight gain profiles, CAS-, SPI- or WPH-fed rats did not differ in development, organ weights, in vitro hepatic metabolism of testosterone (T), or reproductive performance. However, some endocrine-related functions differed between rats fed these proteins. We found that SPI accelerated puberty in female rats (p < .05) and WPH delayed puberty in males and females, as compared with CAS (p < .05). Gender differences were also found in gonadectomy-induced steroid responses. Male rats had normal serum T levels, but female rats fed SPI had reduced serum 17beta-estradiol concentrations and a blunted 17beta-estradiol response to ovariectomy, as compared to rats fed CAS or WHP (p < .05). Female rats fed SPI or WHP or treated with genistein had reduced incidence of chemically induced mammary cancers (p < .05) compared to CAS controls, with WHP reducing tumor incidence by as much as 50%, findings that replicate previous results from our laboratory. Together, these results suggest gender-specific differences in development and certain endocrine responses among rats fed diets composed of a single protein source such as those used in infant formulas. Whether similar developmental effects occur in human infants is unknown, but unlikely because (1) most infants do not consume such diets throughout life as these rats did, and (2) no such effects have been reported in millions of American infants fed infant formula containing these proteins. The long-term health consequence implications of early diet exposure to SPI and WPH, such as reduced breast cancer incidence, are likely to be very positive.

Animals↗