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N A Pampori

Publications and source records attributed to N A Pampori.

At least 19 recordsLinked to original sources
PubMed2001

Infusion of gender-dependent plasma growth hormone profiles into intact rats: effects of subcutaneous, intraperitoneal, and intravenous routes of rat and human growth hormone on endogenous circulating growth hormone profiles and expression of sexually dimorphic hepatic cyp isoforms.

The dramatic sexual dimorphism in rat hepatic CYPs is determined by gender differences in the circulating GH profiles. Accordingly, each responsive isoform of CYP is induced or suppressed by different components, i.e., signaling elements, in the GH profiles. It was the purpose of this study to determine whether the signaling elements in the sexually dimorphic plasma GH profiles identified in GH-depleted rats are recognized by the hepatic CYPs in intact rats exposed to a multiplicity of signals contained in the normal gender-dependent GH profiles. To accomplish this goal, we imposed (via osmotic minipumps) the continuous feminine GH profile upon normal male rats and superimposed (via intra-atrial catheters) the episodic masculine profile upon normal females. Monitored circulating GH profiles indicated that the administered GH had little or no effect on the normally secreted gender-dependent endogenous profiles. Basically, we observed that the degree of constancy of GH in the circulation (continuous in females and episodic in males) is the primary determinant establishing sexually dimorphic expression of eight hepatic CYPs in intact rats. However, the characteristic expression levels of each isoform observed in male and female rat liver are determined by an interaction of more subtle signals in the GH profiles reflected in the concentration and persistence of the feminine continuous profile as well as the frequency, duration, and amplitude of pulse and interpulse periods in the masculine episodic profile. In the course of the study, unexpected findings led us to compare the effectiveness of s.c.- and i.p.-infused GH and rGH with hGH. Briefly, male- and female-dependent hepatic CYPs were undoubtedly most responsive to rGH infused by i.p.-implanted osmotic pumps.

Animals↗
PubMed2000

Nominal growth hormone pulses in otherwise normal masculine plasma profiles induce intron retention of overexpressed hepatic CYP2C11 with associated nuclear splicing deficiency.

Restoration of circulating masculine GH profiles at minipulse amplitudes (i.e. approximately 10% of normal) to hypophysectomized male rats and neonatal administration of monosodium glutamate (MSG), producing a similar plasma GH profile, both result in an overexpression (approximately 200-300%) of CYP2C11 messenger RNA (mRNA), the predominant hepatic cytochrome P450 (CYP) drug-metabolizing enzyme in adult male rats. Coincident with the severalfold elevation in transcript level is a modest 10-30% overexpression of CYP2C11 protein and its catalytic activities. Using hepatic tissue from adult, neonatally MSG-treated rats, we have cloned a variant species of CYP2C11 mRNA containing all of the essential elements of a full-length complementary DNA, including initiating codon, termination codon, and polyadenylase tail. In addition, the transcript contains a 742-bp intervening sequence (identical to the complete terminal intron) between the last and penultimate exons, and an intron-specific oligo probe for Northern blotting demonstrates the presence of the variant transcript in liver of MSG-treated rats. Associated with the overexpression and intron retention of the transcript is a 50% reduction in the nuclear splicing capacity of the liver for model precursor CYP2C11 mRNA. It is proposed that this splicing defect may be a consequence of the mini-GH pulses (secreted in otherwise normal masculine plasma profiles) signaling abnormal processing of precursor CYP2C11 mRNA to produce a substantial portion of intron retained, nontranslatable transcript.

Animals↗
PubMed1999

Gender differences in the responsiveness of the sex-dependent isoforms of hepatic P450 to the feminine plasma growth hormone profile.

Most of the constitutive hepatic P450 isoforms expressed in the rat exhibit dramatic gender differences. Whereas only male hepatocytes contain CYP2A2, 2C11, and 3A2, only female hepatocytes express CYP2C12 and 3- to 4-fold greater levels of CYP2C7. This sexually dimorphic expression of hepatic P450 isoforms is regulated by the gender-dependent secretory GH profiles, i.e. episodic in males and continuous in females. In the case of the feminine GH profile, the continuous presence of the hormone in the circulation completely suppresses male-specific CYP2A2, 2C11, and 3A2, while stimulating full expression of female-dependent CYP2A1, 2C7, 2C12, and non-P450 testosterone 5alpha-reductase (type 1). The gender-dependent expression of the P450s can be reversed by exposing male rats to the continuous feminine plasma GH profile and females to the episodic masculine GH profile. Under these conditions, females will now express the male-specific isoforms and suppress the female-dependent forms, whereas the opposite will occur in the males. Nevertheless, it is not clear whether the levels of expression or suppression are comparable in male and female rats exposed to the same sex-dependent GH profiles. In the present study, we have renaturalized the circulating feminine GH profile in euthyroid-maintained, hypophysectomized female and male rats at six concentrations ranging from 3-100% of normal. Continuous monitoring of GH levels revealed indistinguishable plasma profiles in females and males at each dosage administered. In the case of females, restoration of the feminine-like plasma GH profile at a concentration that was 3% of the normal level restored expression levels (i.e. mRNA, protein, and/or catalytic activity) of female-dependent CYP2C12, 2A1, and 5alpha-reductase to 50% or greater of normal and fully suppressed expression of male-specific CYP2A2, 2C11, and 3A2. Twice the dosage of the hormone (6% of normal) was required to restore female-predominant CYP2C7 to 50% of normal in hypophysectomized female rats. In contrast, we found that all of the measured isoforms were significantly less responsive to the inductive and suppressive effects of the feminine-like GH profile when administered to male rats. While suppression of the male-specific isoforms (i.e. CYP2A2, 2C11, and 3A2) in male rats required concentrations of GH in the feminine profile 2-3 times greater than were effective in female rats, no dosage of the hormone was as effective in inducing female-dependent P450s (i.e. CYP2A1, 2C7, and 2C12) in males as in females. Clearly, the continuous feminine GH profile was more effective at inducing and suppressing gender-dependent isoforms of hepatic P450 when restored to female rats, where it is normally secreted, than in males. As GH profiles appear to be the sole factor responsible for regulating the sexually dimorphic expression of hepatic P450 isoforms in adult rats, the differential responsiveness of male and female rats to the feminine GH profile are likely to be inherently induced by irreversible imprinting during a critical developmental period.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

Feminization of hepatic cytochrome P450s by nominal levels of growth hormone in the feminine plasma profile.

The feminine profile of continuous growth hormone secretion was restored at various concentrations to hypophysectomized, thyroxine-supplemented female rats to determine the minimum signaling concentrations of the hormone required to maintain female-like expression levels of gender-dependent hepatic cytochrome P450s (P450s). Rat growth hormone was infused by intraperitoneally implanted osmotic minipumps, and the resulting circulating concentrations and profiles were determined by radioimmunoassay of serially collected plasma samples. Restoration of feminine growth hormone profiles at 3% of physiological concentration completely suppressed male-specific CYP2C11, CYP2C13, CYP2A2, and CYP3A2. Although significant levels of female-dependent isoforms were expressed at this growth hormone concentration, their full expression required, somewhat higher plasma concentrations of the hormone; CYP2A1 and 5 alpha-reductase were increased to normal female levels with only 6-12% of physiological concentrations of the hormone, normal expression levels of CYP2C12 required approximately 12-25% physiological hormone levels, and CYP2C7 required approximately 25-50% of the normal growth hormone profile to attain female-like expression levels. When determined, protein and specific catalytic activities were in agreement with mRNA levels, supporting the conclusion that growth hormone regulates gender-dependent expression of P450 isoforms by transcription initiation. There was little effect of gender, hypophysectomy, or growth hormone replacement on CYP2C6, growth hormone receptor, and growth hormone-binding protein mRNAs. In contrast, insulin-like growth factor-1 mRNA was sexually dimorphic (male > female), virtually disappeared after hypophysectomy, and was restored to female-like levels with plasma growth hormone concentrations equaling 12-25% of normal. These findings demonstrate the effectiveness of nominal growth hormone concentrations (undetectable by available radioimmunoassay) in an otherwise feminine plasma profile to maintain female-like expression levels of gender-dependent P450s.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1995

Gender differences in drug metabolism regulated by growth hormone.

Gender differences in drug metabolism in rats have been known for more than 60 years when it was first reported that the much shorter duration of drug action in the male was due to the effects of testicular androgens. More recent studies have demonstrated that this sexual dimorphism in rat drug metabolism results from the differential expression of a possible dozen, or so sex-dependent hepatic forms of cytochrome P450. Moreover, it is the sexually dimorphic plasma profiles of growth hormone, and not androgens, that directly regulate the expression of these individual forms of hepatic cytochrome P450. Male rats secrete growth hormone in an "on-off" episodic rhythm in which interpulse periods contain no detectable levels of the hormone. Growth hormone secretion in the female rat is also pulsatile, but can be characterized as "continuous" since hormone levels are always present in the circulation. It would appear that the duration of the interpulse period is at least one "signal" in the growth hormone profile regulating hepatic expression of the sex-dependent forms of cytochrome P450, and thus establishing the gender differences in drug metabolism. The exaggerated gender differences in rat drug metabolism (i.e. 300-500%) have made it the standard, and understandably an ideal model in which to investigate the mechanisms regulating these dimorphisms. However, it is also possible that these studies have limited value when extrapolated to other species, such as humans, in which the magnitude of the sexual differences are much smaller, and the dimorphism may be reversed (F > M). In this regard, the mouse model, in which the sexual differences (F > M) in drug metabolizing enzyme activities vary by only 40-100%, are also regulated by sex-dependent plasma growth hormone profiles, and may be more representative of the vast majority of outbred species in which only subtle gender differences occur in drug metabolism.

Animals↗
PubMed1995

Neonatal phenobarbital-induced defects in age- and sex-specific growth hormone profiles regulating monooxygenases.

Growth hormone was secreted in sexually dimorphic patterns in both 65- and 150-day-old rats (i.e., "on-off" pulsatile for males and "continuous" pulsatile for females), but as a result of a 200-400% increase in pulse levels the mean concentration of hormone in the circulation was about two times as great in the younger animals. Neonatal exposure to phenobarbital at anticonvulsant therapeutic doses for the rat reduced the pulse amplitudes of circulating growth hormone in both the 65- and 150-day-old males but only in the 65-day-old females. As expected, neonatal administration of the barbiturate produced an almost immediate increase in the activities of the hepatic monooxygenases, as measured by hexobarbital metabolism, which declined to noninduction levels after treatment ceased. Contrary to the well-known transient effects of phenobarbital, at around the time of sexual maturity when gender-dependent differences in hepatic monooxygenases appear (males > females), we observed a second "round" of enzyme induction that persisted in both sexes for the remainder of the study (180 days). Because growth hormone is the primary regulator of sex-dependent hepatic monooxygenases, we have proposed that the abnormal plasma growth hormone profiles produced by neonatal phenobarbital are responsible for the permanent induction of hepatic monooxygenases.

Aging↗
PubMed1995

Growth hormone regulation of male-specific rat liver P450s 2A2 and 3A2: induction by intermittent growth hormone pulses in male but not female rats rendered growth hormone deficient by neonatal monosodium glutamate.

Growth hormone (GH) secretory patterns regulate the expression of several sex-dependent liver cytochrome P450 (CYP) genes. Studies using the hypophysectomized rat model have established that the intermittent plasma GH secretory pattern associated with adult male rats markedly stimulates liver expression of the male-specific CYP 2C11, a testosterone 2 alpha- and 16 alpha-hydroxylase, but is not required for expression of other male-specific liver enzymes, including CYP 2A2, a testosterone 15 alpha-hydroxylase, and CYP 3A2, a testosterone 6 beta-hydroxylase. In the present study, the effects of intermittent GH treatment on liver CYP expression were studied in adult rats rendered GH deficient by neonatal administration of monosodium glutamate (MSG), which depletes circulating adult GH without the global loss of other pituitary-dependent hormones that is associated with hypophysectomy. Restoration of the normal masculine circulating GH profile of six daily pulses (180-225 ng GH/ml/peak) in MSG-treated male rats by the use of an external pumping apparatus led to a substantial (30-50%) restoration of normal male levels of CYP 2A2 and CYP 3A2 activity, protein, and mRNA. GH pulsation at the nonphysiological frequencies of two or four times per day was less effective unless given at a dose that resulted in supraphysiological plasma GH levels. Although intermittent GH treatment can induce male-specific P450 expression in hypophysectomized female rats, the same hormone treatment did not stimulate CYP 2A2 or CYP 3A2 expression in MSG-treated female rats. Liver GH receptor mRNA levels at adulthood were not significantly altered by neonatal MSG treatment, suggesting that the unresponsiveness of MSG-treated females and the previously reported low responsiveness of MSG-treated males to GH-induced CYP 2C11 expression are not due to the absence of GH receptor. Moreover, normal liver IGF-1 mRNA levels were expressed in the MSG-treated female rats, suggesting that the liver GH receptor is functional in these animals. The present findings establish that the adult male-specific enzymes CYP 2A2 and CYP 3A2 can be positively regulated by intermittent GH pulsation despite their GH-independent expression in hypophysectomized rats. Moreover, neonatal MSG treatment, particularly in female rats, may lead to the loss of factors other than GH that are required for full expression of the pulsatile GH-stimulated CYP 2A2, 3A2, and 2C11 genes.

Animals↗
PubMed1994

Subnormal concentrations in the feminine profile of circulating growth hormone enhance expression of female-specific CYP2C12.

When newborn female rats were treated with monosodium glutamate, 4 mg/g body weight, on days 1 and 3 of life, circulating growth hormone concentrations were permanently reduced 75-85% in adulthood, whereas the feminine secretory profile characterized by frequent growth hormone pulses, separated by short-lived, measurable troughs, persisted. Associated with this reduction in growth hormone secretion was a mild obesity and a slight depression in peripubertal body weight. In contrast, expression of growth hormone-dependent, female-specific CYP2C12 was increased by almost 100% when measured at both its protein and mRNA levels. In agreement, this supraphysiological expression of CYP2C12 was reflected at a pharmacologic level by a simultaneous elevation in in vitro and in vivo hexobarbital metabolism. When growth hormone secretion was pulsatile (i.e. masculine) or was eliminated from the circulation (i.e. hypophysectomy), hepatic CYP2C12 protein and mRNA were undetectable. The present findings suggest that the normal levels of plasma growth hormone found in female rats are not necessarily optimum for the expression of female-specific CYP2C12.

Animals↗
PubMed1994

Effects of neonatally administered monosodium glutamate on the sexually dimorphic profiles of circulating growth hormone regulating murine hepatic monooxygenases.

Neonatal male and female mice were treated with monosodium glutamate (MSG) at either 2.0 or 4.0 mg/g body weight on alternate days during the first 9 days of life. As adults, mice were catheterized to obtain unstressed, serial blood samples for the determination of ultradian profiles of circulating growth hormone. In addition, monooxygenase levels (i.e. steroid hydroxylases and drug-metabolizing enzymes) were measured in hepatic microsomes. Generally, both doses of MSG produced the same developmental defects. Mice neonatally exposed to the amino acid developed a syndrome characterized by retarded growth, obesity and reduced organ weights. While vehicle-treated mice secreted growth hormone in sexually dimorphic patterns defined by pulse frequency (i.e. F > M), hormone concentrations in plasma samples obtained during 8 continuous hr of serial blood collections from both male and female MSG-treated mice were barely detectable at best, and exhibited no pulsatility. Approximately 15% of the measured monooxygenases were male-predominant, 35% were female-predominant and 50% had no sex differences. The enhanced expression of the hepatic monooxygenases in response to MSG-induced depletion of plasma growth hormone indicates that the hormone basically functions as a suppressor of the murine enzyme system.

Age Factors↗
PubMed1994

Growth hormone-dependent and -independent sexually dimorphic regulation of phenobarbital-induced hepatic cytochromes P450 2B1 and 2B2.

Sexually dimorphic regulation of phenobarbital-induced cytochromes P450 2B1 and 2B2 (collectively referred to as P450 2B) as well as P450 2B-dependent monooxygenase activities was studied in multi-hormone-depleted hypophysectomized rats and in growth hormone (GH)-deficient monosodium glutamate (MSG)-treated rats. Our results indicate that endogenous GH suppresses phenobarbital induction of P450 2B and that the feminine pattern of continuous GH secretion is more suppressive than the masculine profile of episodic secretion. Moreover, we have found that it is the height of the GH pulse, and not necessarily its frequency nor the interpulse trough periods, that signals the suppressive effects of GH on P450 2B expression in male rats. Last, irrespective of the presence or absence of circulating GH, the magnitude of phenobarbital induction of P450 2B and associated monooxygenases was consistently lower in female rats, suggesting the presence of some degree of sex-dependent, but GH-independent regulation.

Animals↗
PubMed1994

Testicular regulation of sexual dimorphisms in the ultradian profiles of circulating growth hormone in the chicken.

Ultradian patterns in plasma growth hormone (GH) concentrations were determined in adult white Leghorn roosters, hens and capons. Serial blood samples were collected every 15 min over 8 h through surgically placed chronic indwelling right atrial catheters and assayed for GH content by a GH content by a homologous radioimmunoassay. In both sexes, GH levels fluctuated episodically, with peak and interpeak periods each lasting about 45 min in both roosters and hens. However, GH concentrations in the peaks and nadirs were 2.5-3.5 times greater in the plasma GH profiles of roosters as compared to hens, which resulted in roosters having higher mean GH concentrations. Caponizing completely feminized the episodic GH secretory profile. In contrast to chickens, the common sexually dimorphic feature in secretory GH profiles of mammals is the enhanced peak frequencing found in females.

Activity Cycles↗
PubMed1994

Over-expression of CYP2C11, the major male-specific form of hepatic cytochrome P450, in the presence of nominal pulses of circulating growth hormone in adult male rats neonatally exposed to low levels of monosodium glutamate.

Male rat pups were injected with monosodium glutamate (MSG), 4 mg/g b.wt., on either days 1 and 3 or days 1, 3, 5, 7 and 9 of life. Plasma samples obtained during 8.5 continuous hr of serial blood collections from adults, neonatally treated with five doses of MSG, contained no detectable concentrations of growth hormone. In addition, the livers of these animals contained no measurable expression levels of the major male-specific form of cytochrome P450 (CYP2C11) mRNA or its protein. In contrast, adult male rats treated with only two neonatal injections of MSG exhibited typical masculine profiles of growth hormone release, except that the amplitudes of the ultradian pulses were reduced to about 10 to 20% of normal male levels. Otherwise, like control males the peaks occurred about every 3.5 to 4 hr and the intervening 3-hr troughs had undetectable concentrations of growth hormone. Moreover, the livers of these twice-injected MSG-treated rats over-expressed CYP2C11 as indicated by a 200% increase in CYP2C11 mRNA and a concomitant 30 to 40% increase in CYP2C11 protein and its catalytic activities. The effectiveness of minipulses of growth hormone, mimicking the pattern found in MSG-treated animals, to induce over-expression of hepatic CYP2C11 in hypophysectomized rats, suggests that the supraexpression of CYP2C11 found in the MSG-treated animals may be explained, in part, by the abnormal profiles of circulating growth hormone induced by neonatal exposure to the amino acid. In conclusion, depending upon neonatal exposure levels, MSG can produce permanent, yet very different defects in the adult male patterns of growth hormone secretion and growth hormone-dependent CYP2C11 expression.

Animals↗
PubMed1993

Sexual dimorphism in avian hepatic monooxygenases.

Adult white Leghorn chickens exhibited a sexual dimorphism in hepatic microsomal monooxygenases determined from the concentrations of total cytochromes P450 and b5, and the metabolism of drug (hexobarbital, coumarin and ethoxyresorufin) and steroid (androstenedione and testosterone) substrates that were 2- to 4-fold greater in roosters than in hens. Caponizing at 6 weeks of age reduced the activities of the monooxygenases to levels comparable to those found in intact hens. In spite of the fact that testosterone replacement maximally stimulated comb growth in the capons and elevated (i.e. masculinized) hepatic monooxygenase activities in the hens to male-like levels, androgen replacement was ineffective in increasing the subnormal enzyme levels in the capons. While the failure of testosterone administration to restore monooxygenase levels in the capons may be explained by the immaturity of the birds at orchiectomy, the present results demonstrate, that like some mammals, birds may display gender differences in hepatic monooxygenases that are regulated by the testes.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1993

Irreversible suppression of growth hormone-dependent cytochrome P450 2C11 in adult rats neonatally treated with monosodium glutamate.

Neonatal exposure to monosodium glutamate (MSG) permanently blocks growth hormone (GH) secretion, which results in the development of a well-defined syndrome characterized by stunted body growth, obesity and impaired drug metabolism. We have found that restoration of the normal masculine circulating profile of GH (i.e., six daily pulses) by use of an external pumping apparatus is ineffective in restoring the normal expression of hepatic cytochrome P450 2C11, a major GH-dependent drug and steroid metabolizing enzyme that is eliminated by MSG treatment. Moreover, administering GH at two, four or seven plasma pulses per day with amplitudes ranging from physiologic to 7 times normal were similarly ineffective in restoring the expression (at both an activity and mRNA level) of the cytochrome. Additionally, multicytochrome P450-dependent hexobarbital hydroxylase was also unresponsive to GH administration in the MSG-treated rats. Because GH replacement was unable to correct the enzyme defects, our results suggest that the developmental abnormalities produced by neonatal MSG are not simply a result of a GH deficiency per se, but are due to an irreversible insensitivity of the target cell to GH.

Animals↗
PubMed1991

Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450.

Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomized rats pulses of rat GH of varying frequency and amplitude, a critical element for liver discrimination between male and female GH patterns was identified. Liver expression of the male-specific steroid 2 alpha (or 16 alpha)-hydroxylase P450, designated CYP2C11, was stimulated by GH at both physiological and nonphysiological pulse amplitudes, durations, and frequencies, provided that an interpulse interval of no detectable GH was maintained for at least 2.5 hr. This finding suggests that hepatocytes undergo an obligatory recovery period after stimulation by a GH pulse. This period may be required to reset a GH-activated intracellular signaling pathway or may relate to the short-term absence of GH receptors at the hepatocyte surface after a cycle of GH binding and receptor internalization. These requirements were distinguished from those necessary for the stimulation by GH of normal male growth rates in hypophysectomized rats, indicating that different GH responses and, perhaps, different GH-responsive tissues recognize distinct signaling elements in the sexually dimorphic patterns of circulating GH.

Activity Cycles↗
PubMed1991

Differential effects of neonatally administered glutamate on the ultradian pattern of circulating growth hormone regulating expression of sex-dependent forms of cytochrome P450.

Neonatal male rats were treated with monosodium glutamate (MSG) at either 0.5, 1.0, 2.0, 3.0 or 4.0 mg/g body weight on alternate days during the first 9 days of life. As adults, rats were catheterized to obtain unstressed, serial blood samples for the determination of ultradian patterns of circulating growth hormone. In addition, the levels of drug-metabolizing enzymes (i.e. hexobarbital hydroxylase, cytochromes P450 and b5, NADPH-cytochrome P450 reductase and ethoxyresorufin O-deethylase) as well as sex-dependent forms of cytochrome P450 [i.e. male-dependent cytochromes P450 2c (IIC11), 2a (IIIA2) and RLM2 (IIA2) and female-dependent cytochromes P450 2d (IIC12) and 3 (IIA1)] and/or their catalytic activities were measured in the hepatic microsomes of the treated rats. The results demonstrated a dose-dependent, graded response to MSG treatment. As the dose of MSG increased from 0.5 to 4.0 mg, there was a concurrent decline in the amplitudes of the characteristically masculine, episodic bursts of growth hormone, until at the highest dose (4 mg), the pulses were no longer detectable. Associated with this dose-dependent alteration in the ultradian pattern of growth hormone secretion was a measurable change in the activities of the sex-dependent hepatic enzymes. As the pulse heights of the hormone declined to 10-20% of their normal amplitudes, the levels of the male-dependent enzymes (i.e. the drug-metabolizing enzymes, as well as the male forms of cytochrome P450 and their specific steroid hydroxylases) were maintained, and in some cases, exceeded the levels normally found in males. However, as the hormone pulse heights declined, there appeared an accompanying increase in the activities of some of the female-dependent enzymes. Finally, with the loss of all detectable levels of circulating growth hormone, the normal masculine profile of hepatic enzymes was reversed to an apparently normal (with the exception of cytochrome P450 2d) feminine profile. Summarizing, the results indicate that (1) neonatal administration of MSG can produce dose-dependent, graded, long-term developmental defects in the ultradian rhythm of circulating growth hormone and associated sex-dependent hepatic enzymes, and (2) while the male-dependent hepatic enzymes can be maintained at normal or even higher levels in the face of an up to 90% reduction in the pulse heights of plasma growth hormone, the activities of the female-dependent enzymes may begin to increase.

Animals↗