On the obligatory role of the hypophysis in sexual differentiation hepatic metabolism in rats.

The hepatic metabolism of 4-[4-14C]androstene-3,17-dione and 5alpha-[4-14C]androstane-3alpha,17beta-diol was studies in castrated and hypophysectomized male rats with a transplanted pituitary under the kidney capsule. The effects of testosterone propionate and estradiol benzoate on liver metabolism were also studied in these experimental animals. It was found that the autonomous pituitary secreted a "feminizing factor" that transformed the male type of steroid metabolism characteristic of hypophysectomized rats into a female type of metabolism Hypophysectomized rats were unresponsive towards androgen action on the liver and did not respond with feminized hepatic metabolism after treatment with estradiol benzoate. It is concluded that estrogenic action on liver enzymes is mediated via modulation of the secretion of a central (probably hypothalamic) "feminizing factor inhibiting factor" and the sex hormonal effects of hepatic metabolism only occur in the presence of a pituitary in situ.     

Aldosterone metabolism in the isolated perfused liver of female and male rats

A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-[4-14C]aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate [4-14C]aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes. Perfusate 4-14C-labeled radiometabolites after 90 min of perfusion were lower in livers of castrated male rats than in noncastrated male rats (P less than 0.001). The final perfusate 14C-labeled radiometabolite concentration correlated inversely with the total 14C in bile (P less than 0.01). All 14C-labeled radiometabolites detected in perfusate and bile after 90 min were more polar than aldosterone. After enzymatic hydrolysis, some of the metabolites from the male livers cochromatographed with tetrahydro- and dihydroaldosterone, while other fractions remained more polar. Only more polar metabolites were detected in the perfusate and bile of female livers.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of liver regeneration on hepatic cytochrome P450 isozymes and serum sex steroids in the male rat

Partial hepatectomy in male adult rats results in raised serum estrogen levels and demasculinization of certain aspects of hepatic metabolism. Some constitutive forms of hepatic cytochrome P450 are sex-dependent and we have previously demonstrated demasculinization of cytochrome P450 isozyme distribution in a rat model of cirrhosis. As liver regeneration is an integral component of cirrhosis, the present study was performed to ascertain the effects of regeneration on hepatic cytochrome P450 isozyme composition and serum sex steroid concentrations. Adult male rats were subjected to 65% partial hepatectomy or sham-operation. The position-specific hydroxylation of androstenedione was used as a probe for isozyme activity. Serum sex steroids, hepatic enzymes, and hepatic deoxyribonucleic acid synthesis were measured in groups of animals at 0, 6, 24, 48, and 72 h. By 72 h total microsomal cytochrome P450 in partially hepatectomized animals had fallen to 66% of that in nonoperated animals. In both partially hepatectomized and sham-operated animals, androstenedione 7 alpha- and 16 beta-hydroxylase activity returned to preoperative levels by 48 h. However, the male-specific androstenedione 16 alpha- and 6 beta-hydroxylase activities and aromatase activity remained suppressed in partially hepatectomized liver. Serum estradiol increased eightfold in partially hepatectomized rats and peaked at 6 h followed by a gradual fall to control values. No change in serum estradiol was observed in sham-operated animals. We conclude that demasculinization of hepatic oxidative metabolism occurs in regenerating rat liver. The early rise in serum estradiol is consistent with a role for this hormone in the changes in cytochrome P450 observed, and possibly the process of liver regeneration.     

An unusual estrogen-binding liver protein and the dynamics of sex steroids: estrogen stimulation of testosterone metabolism in the male rat in vivo

A study was made of the influence of estrogens on the nature of 3H-testosterone metabolism in the liver of male and female rats. Estradiol stimulation of intensity and modulation of character of testosterone metabolism in the liver of male rats were demonstrated by thin layer chromatography. A simultaneous increase in the level of radioactivity of testosterone and its metabolites was noted in the liver and blood serum. The role of the unusual estrogen binding protein (UEBP) as a mediator in this estradiol action was demonstrated by the hormonal specificity of the efficacy of estrogens corresponding to the specificity of their affinity to UEBP. In female rats estradiol inhibited testosterone metabolism. Taking account of the data obtained UEBP possible functions with relation to the regulation of sex steroid metabolism were analysed.     

Effects of morphine and naloxone on inhibition by ovarian hormones of pulsatile release of LH in ovariectomized rats

The purpose of this study was to determine the effects of morphine and naloxone on pulsatile release of LH in ovariectomized rats treated (or untreated) with ovarian steroids. Ovariectomized rats were given a subcutaneous injection of estradiol benzoate (20 micrograms) or estradiol benzoate (20 micrograms) and progesterone (10 mg) 3 days prior to experimentation. The rats were then given intravenous injections of naloxone (2 mg/kg), morphine (5 mg/kg), or 0.87% NaCl every hour for 3 h. For LH assays, 0.3 ml blood was collected via an atrial cannula 15 min after drug treatment and every 15 min thereafter for 3 h. Pulsatile LH release was suppressed by estradiol benzoate or the combination of estradiol benzoate and progesterone. Naloxone was able to counteract inhibition of pulsatile LH release by these steroids. These results suggest that the endogenous opioid peptides are involved in the negative feedback exerted by estrogen and progesterone on pulsatile LH release. Morphine had no effect on steroid inhibition of pulsatile LH release.     

Cortisol metabolism in lymphocytes from cancer-bearing patients

A study was conducted to determine the pattern of cortisol metabolism by lymphocytes obtained from four groups of subjects: 27 male and female patients suffering from various types of malignancy other than malignancy of lymphatic tissues; and 26 healthy male and female controls. Known concentrations of cells were incubated with 1,2-³H-cortisol and the products were isolated by thin-layer and paper chromatography. Three metabolites were found to be produced by lymphocytes from both normal and cancer-bearing patients: 20α-hydroxycortisol, 20β-hydroxycortisol, and tetrahydrocortisol. Cells from the female control group were found to be more active than those from the male controls, while cells from cancer-bearing patients were markedly more active than the normal cells, regardless of sex. It is suggested that this finding of increased metabolism of cortisol by lymphocytes from patients with different types of malignancy other than lymphoma may provide the basis for a new diagnostic aid.     

Neuroendocrinological effects of ketoconazole in rats

The effect of ketoconazole on steroid synthesis was studied in intact (sham-operated) and castrated male and ovariectomized female rats. Rats were given 25 mg/kg ketoconazole twice a day im for 5 days. The influence of ketoconazole was also investigated on hormone release altered by GnRH, estradiol and haloperidol. The following hormones were measured: serum LH, PRL, testosterone, corticosterone, 17-OH-progesterone, estradiol, and dopamine content of the tubero-infundibular area. Ketoconazole treatment resulted in a significant decrease of testerone level (from 7.93 +/- 1.99 to 3.83 +/- 0.94 nmol/l), whereas LH, PRL, corticosterone and 17-OH-progesterone remained unchanged in the male rat. The effect of castration on LH level was reduced by ketoconazole in male (from 590 +/- 35 to 390 +/- 25 micrograms/l) and female rats (from 468 +/- 22 to 346 +/- 39 micrograms/l), but the GnRH-stimulated LH release in castrated and ovariectomized animals was unchanged. The suppressive action of estradiol on LH in ovariectomized rats was enhanced (from 160 +/- 41 to 64.6 +/- 12.9 micrograms/l), and its priming effect on PRL release was diminished by ketoconazole (from 598 +/- 81 to 281 +/- 66 micrograms/l). Ketoconazole failed to modify the tubero-infundibular dopamine content and haloperidol-induced PRL release. It can be assumed that in addition to its inhibitory role of steroid biosynthesis ketoconazole has an influence on central mechanisms underlying LH and PRL release.     

The regulation of oxytocin receptor binding in the ventromedial hypothalamic nucleus by testosterone and its metabolites.

Oxytocin (OT) receptor binding in the ventromedial hypothalamic nucleus is regulated by testosterone (T) in male rats. However, T is metabolized in the brain, and many of the central effects of T are mediated by its metabolites. The experiments reported here were designed to determine whether T affects OT receptor binding directly or through the action of its metabolites 17 beta-estradiol and 5 alpha-dihydrotestosterone. Adult male rats were either sham operated or castrated and treated 1 week later with T propionate (TP), 17 beta-estradiol benzoate (EB), dihydrotestosterone benzoate (DHTB), DHTB plus EB, or oil. OT receptor binding was assessed autoradiographically using [125I]d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT. In addition, seminal vesicle weights were measured as an index of androgenic activity. These experiments showed that TP and DHTB plus EB increased OT receptor binding in the ventromedial hypothalamic nucleus to the levels in intact males. Treatment with EB alone partially reinstated binding to the levels in intact males, while DHTB treatment was without effect. Castrated males treated with either TP or DHTB had seminal vesicle weights comparable to those of gonadally intact males and greater than those of animals in all other steroid conditions, indicating that sufficient levels of circulating steroids were attained in these groups. These data suggest that the induction of hypothalamic OT receptor binding by T is the result of the combined actions of estradiol and dihydrotestosterone. However, the mechanism underlying this interaction is unknown.     

The possible involvement of intestinal bacteria in steroidal hypertension

The bacterial flora of rats ws modified, using antibiotics, in order to interrupt the enterohepatic circulation of steroids excreted in bile. Antibiotic treatment was contined while corticosterone was administered to these animals, and over five days corticosterone raised blood pressures by an average of 9.2 mmHg compared with 24.6 mmHg in rats given steroid alone. These findings are consistent with the possibility that in normal rats bacterial metabolites of steroids, when reabsorbed in the enterohepatic circulation, contribute to the physiological response to exogenous steroids.     

Hypothalamo-pituitary regulation of cytochrome P-450(15) beta apoprotein levels in rat liver

The regulation of the sexually differentiated steroid sulfate 15 beta-hydroxylase, cytochrome P-450(15) beta of female rat liver has been investigated. Specific antibodies raised to isozyme P-450(15) beta were used with the Western blot technique to quantitate the specific levels of P-450(15) beta in liver microsomes. The method demonstrated that the levels of the protein are about 16-fold higher in female than in male microsomes and also showed that the specific microsomal content of P-450(15) beta is controlled by GH. Hypophysectomy of female animals resulted in a decrease of P-450(15) beta to male levels. Continuous infusion of human GH, mimicking the female pattern of GH secretion in intact male animals, caused an elevation of the P-450(15) beta level to that of the female. The same dose of human GH in hypophysectomized male or female animals raised the P-450(15) beta level 8-fold or 50% of that seen in normal females. Infusion of ovine PRL to intact male rats had no effect on P-450(15) beta levels, whereas infusion of rat GH caused a 4-fold increase. Thus, the regulation of P-450(15) beta by GH is mainly associated with the somatogenic properties of the hormone. Furthermore, sc injection of rat GH every 12 h, mimicking the male pattern of GH secretion, had no effect on P-450(15) beta levels, demonstrating the importance of the GH secretory pattern in regulation of the specific protein levels. Postpubertal castration of male animals did not influence the microsomal P-450(15) beta content, whereas neonatal castration led to a feminization of the P-450(15) beta content in the adult male rat. Administration of estradiol valerate to male animals caused complete feminization of P-450(15) beta levels, whereas administration of androgen to female animals caused a decrease to male levels. Before 21 days of age, the P-450(15) beta level was slightly higher in male than in female rats. At 35 days, however, the P-450(15) beta level in female rats had increased almost 100-fold, whereas the levels in males increased only slightly. These changes are concomitant with the development of the sexual differentiation of the GH secretory pattern, supporting the role of GH in P-450(15) beta regulation. In conclusion, isozyme P-450(15) beta is a GH-regulated enzyme specific for female rats. The low level of the protein in males is probably explained by neonatal androgenic programming of the GH secretory pattern.     

Testosterone and dihydrotestosterone, but not estradiol, selectively maintain pituitary and serum follicle-stimulating hormone in gonadotropin-releasing hormone antagonist treated male rats

Recently it has been found that testosterone can maintain and restimulate serum and pituitary follicle-stimulating hormone (FSH) in the gonadotropin-releasing hormone (GnRH) antagonist treated adult male rat. The present investigation was undertaken to determine (1) which metabolite of testosterone, dihydrotestosterone (DHT), or estradiol accounts for the effects of testosterone in GnRH antagonist suppressed rats and (2) whether these effects of testosterone are influenced by other testicular factors. Eight groups of 6-8 adult male Sprague-Dawley rats were subjected to the following treatments: vehicle, GnRH antagonist (75 micrograms/day s.c.), testosterone-filled Silastic implants (3 x 5 cm, s.c.), DHT-filled Silastic implants (3 x 5 cm, s.c.), estradiol benzoate (15 micrograms/day s.c.), and combined administration of GnRH antagonist with either steroid. In addition, the GnRH antagonist/testosterone treatment regimen was applied to rats orchidectomized 72 h prior to initiation of treatments. After 3 weeks of treatment, serum was analyzed for concentrations of luteinizing-hormone (LH), FSH, testosterone, DHT, and estradiol. Pituitary extracts were analyzed for LH and FSH content. Except for the vehicle-treated groups, serum and pituitary LH concentrations were markedly suppressed by all treatments. In intact rats treated with GnRH antagonist alone and/or estradiol, the pituitary FSH level was reduced by more than 70% relative to controls, while both testosterone and DHT maintained pituitary FSH. Similarly, testosterone and DHT, but not estradiol, delayed the decline of serum FSH induced with GnRH antagonist alone. In orchidectomized animals, testosterone was also capable of preventing a reduction of pituitary FSH despite concomitant GnRH antagonist administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maintenance by L-DOPA treatment of estrous cycles and LH response to estrogen in aging female rats

Nineteen, non-cycling female rats, 13–15 months of age, were fed 125 mg L-DOPA/15 g feed daily, and nineteen control rats of the same age were provided feed without L-DOPA. Sixteen of the L-DOPA fed rats each demonstrated 1–7 (average = 3) vaginal estrous cycles during the 75-day period of treatment, whereas no cycles were observed in the untreated controls. All animals were then ovariectomized and the post-castration rise in LH was monitored. Four weeks after ovariectomy, serum LH levels in the L-DOPA treated old female rats were significantly higher than in the non-treated old female rats. A single injection of 20μg of estradiol benzoate (EB) significantly lowered serum LH in the L-DOPA treated rats, but no effect was observed in the non-treated controls. A second injection of EB three days later produced a significantly greater LH surge in the old rats given L-DOPA than in the non-L-DOPA treated controls. These results indicate that prolonged L-DOPA administration can partially prevent the decline in function of the hypothalamo-pituitary-ovarian system in aging female rats.     

Immunoreactive dynorphin is regulated by estrogen in the rat anterior pituitary

The pituitary and hypothalamic content of dynorphin was determined by radioimmunoassay and characterized by high-performance liquid chromatography (HPLC) in adult female Sprague-Dawley rats, intact and ovariectomized with and without estrogen treatment. Animals were given estradiol benzoate, or vehicle (oil) by six daily intramuscular injections. Anterior pituitary content of immunoreactive (ir)-dynorphin in ovariectomized rats was approximately twice that of intact animals, and consisted of a single HPLC peak co-eluting with dynorphin 32. Administration of estradiol benzoate (0.06-6 micrograms/day) caused a marked decrease of ir-dynorphin in the anterior lobe of castrate female rats, with a half-maximal effect at 0.2 microgram/day; levels were restored to those seen in intact animals with 6 micrograms estradiol benzoate per day, an effect which was not influenced by concomitant administration of progesterone (1 mg/day), or bromocriptine (100 micrograms/day). In the hypothalamus and neuro-intermediate lobe multiple peaks of immunoreactive dynorphin were seen, coeluting with dynorphin A 1-8, dynorphin A 1-17 and dynorphin 32. Neither castration nor estrogen treatment altered ir-dynorphin content in these tissues. These findings suggest that the ovary exerts a specific modulating influence on AP ir-dynorphin in the rat, and that in addition this inhibition appears to be mediated by ovarian estrogen.     

Genetic regulation of hepatic steroid 16 alpha-hydroxylase activities in inbred strains of mice

Steroid 16 alpha-hydroxylase activities and properties were studied in C57Bl/6J, 129/J, AKR/R, DBA/2J, C3H/I, and BALB/c mouse liver using four different substrates. The highest enzymatic activities were measured in the female mice, with the exception of the 129/J females. As in the rat liver, the sexual differentiation of the steroid 16 alpha-hydroxylation observed in adult male and female mice took place at puberty. In the adult mouse liver, two steroid 16 alpha-hydroxylase activities (forms I and II) could be differentiated on the basis of their relative affinities for the various steroid substrates and their relative proportions in male and female mouse livers. In the immature mouse liver, no sexual differences could be detected, and the mice of both sexes presented phenotypes identical to those of the adult female. The adult 129/J females appeared genetically deficient with respect to the form I of the steroid 16 alpha-hydroxylase and presented a phenotype identical to that of the adult male mice of the various strains tested. Differences in hydroxylase activities between the C57Bl/6J and 129/J strains were investigated using standard genetic breeding protocols. Steroid 16 alpha-hydroxylase seemed to be inherited additively in the liver of the female mice obtained by crossing the C57Bl/6J male and the 129/J female or the 129/J male and the C57Bl/6J female. In the male mice, regardless of genotype, the observed phenotype was always identical to the two male parental types. Both hormonal and genetic regulations were responsible for the different phenotypes occurring in adult male and female C57Bl/6J and 129/J mouse livers.     

Inhibitory effect of the ovaries on neonatal androgen imprinting of growth hormone secretion in female rats

The effect of neonatal androgen treatment on the GH secretory pattern was examined in intact and ovariectomized adult female rats. Neonatal ovariectomy or sham operation was performed at 1-2 days of age; thereafter, the animals were immediately given testosterone propionate (250 micrograms) or vehicle. Other rats, also treated neonatally with testosterone, were ovariectomized 15-22 days before blood sampling. Plasma GH was measured in blood samples obtained from indwelling intraatrial cannulae every 20 min for 8 h when the animals were 100-140 days old. Plasma GH secretory patterns were analyzed by a pulse analysis computer program (PULSAR). Neonatal testosterone treatment did not affect the GH secretory pattern of female rats with intact ovaries. In contrast, neonatal androgen treatment enhanced GH pulse height as well as mean GH concentration in neonatally ovariectomized female rats to levels comparable to those in intact male rats. Neonatal testosterone administration also significantly increased GH pulse height and mean plasma GH concentration in female rats that were ovariectomized during adulthood. However, the GH secretory pattern of ovariectomized female rats given testosterone neonatally still differed markedly from that of normal males, in that GH pulses occurred less regularly and baseline levels were higher. Pituitary GH content and concentration in neonatally ovariectomized female rats were increased to levels indistinguishable from those in male rats by neonatal testosterone treatment. No significant effect of neonatal testosterone was observed in sham-operated females. Neonatal ovariectomy decreased basal plasma GH levels, but did not affect plasma GH pulse height or pituitary GH levels. The serum estradiol concentration was markedly decreased in ovariectomized female rats, but was unchanged in sham-operated rats given neonatal testosterone, raising the possibility that serum estradiol secretion mediated the antagonistic effect of the ovaries on neonatal androgen imprinting. These results indicate that the presence of ovaries can prevent the stimulatory effect of neonatal androgen exposure on GH storage and secretion in adult female rats.     

Difference in the responsiveness of old female rats to estrogen to secrete sex attractants as a function of different reproductive states

Two age groups of Long-Evans rats (young: 3.5-7 months of age and old: over 23 months of age) were ovariectomized and implanted subcutaneously with a 1:2 estradiol benzoate (E2)-cholestrol mixture-filled Silastic capsule. Olfactory preference of male partners to these female rats over ovariectomized young rats without E2 replacement was examined. Olfactory preference of adult male rats as indicated by investigation frequency and investigation time for old pseudopregnancy (PSP) rats and long-term ovariectomized rats was decreased but not that of prolonged-vaginal-cornification (PVC) rats when compared with young female rats. These results indicate that the responsiveness of old PVC rats to estrogen to secrete sex attractants is not decreased but that of PSP rats and long-term ovariectomized rats is decreased when compared with young female rats.     

Microcirculatory responses to estradiol benzoate in chronic liver damage induced by carbon tetrachloride in the rat

Microcirculatory responses to estradiol benzoate (ES) under condition of chronic liver damage induced by long-term administration of carbon tetrachloride (CCl4) was investigated in the rat. One hundred and five male rats were divided into the following groups receiving 0.1 mg/100 g body weight ES injected intraperitoneally 5 times per week: controls, exposed to CCl4 alone; rats treated with ES from the fourth week of CCl4 exposure; animals treated with ES from the 11th week of CCl4 exposure. In rats receiving CCl4 alone, liver cirrhosis was induced by 10 consecutive weeks of exposure. Microangiograms of the liver demonstrated conspicuous rarefaction of the vascular tree. On the other hand, animals treated with ES had neither atrophic liver nor rarefaction of the intrahepatic vascular tree. ES produced also intrahepatic neovascular proliferation in the cirrhotic liver. After long-term CCl4 administration, ES treated rats had extremely enlarged nodules with tumor-stain like findings, giving rise to a structure differing from hepatocellular carcinoma which latter generally displays a broom-swept appearance. It is concluded that in providing potent angiogenesis in the liver, ES protects the liver against microcirculatory dearangement and parenchymal damage induced by CCl4.     

Bile duct destruction by 4,4'-diaminodiphenylmethane does not block the small hepatocyte-like progenitor cell response in retrorsine-exposed rats

Liver regeneration after surgical partial hepatectomy (PH) in retrorsine-exposed rats is accomplished through the outgrowth and expansion of small hepatocyte-like progenitor cells (SHPCs). The cells of origin for SHPCs and their tissue niche have not been identified. Nevertheless, some investigators have suggested that SHPCs may represent an intermediate or transitional cell type between oval cells and mature hepatocytes, rather than a distinct progenitor cell population. We investigated this possibility through the targeted elimination of oval cell proliferation secondary to bile duct destruction in retrorsine-exposed rats treated with 4,4'-diaminodiphenylmethane (DAPM). Fischer 344 rats were treated with 2 doses (30 mg/kg body weight) retrorsine (at 6 and 8 weeks of age) followed by PH 5 weeks later. Twenty-four hours before PH, select animals were given a single dose of DAPM (50 mg/kg). Treatment of rats with DAPM produced severe bile duct damage but did not block liver regeneration. Oval cells were never seen in the livers of DAPM-treated retrorsine-exposed rats after PH. Rather, liver regeneration in these rats was mediated by the proliferation of SHPCs, and the cellular response was indistinguishable from that observed in retrorsine-exposed rats after PH. SHPC clusters emerge 1 to 3 days post-PH, expand through 21 days post-PH, with normalization of the liver occurring by the end of the experimental interval. CONCLUSION: These results provide direct evidence that SHPC-mediated liver regeneration does not require oval cell activation or proliferation. In addition, these results provide strong evidence that SHPCs are not the progeny of oval cells but represent a distinct population of liver progenitor cells.     

Estradiol modulation of oxytocin binding in the ventromedial hypothalamic nucleus of male and female rats

It has been suggested that estradiol and oxytocin (OT) may interact as neuroendocrine components in the regulation of sexual behavior. In the present study the effect of estradiol benzoate (EB) treatment (50 micrograms/kg body weight/2 days) on [3H]-OT binding was evaluated in adult and 21-day-old gonadectomized male and female rat brains. Coronal sections through the ventro-medial nucleus of the hypothalamus (VMN) were analyzed in three different section planes. EB priming induced an increase in [3H]-OT binding in the VMN of both male and female rats. Greater binding site density and significant EB effects were found in the most caudal plane where the ventrolateral portion of the VMN is well defined at both ages. OT binding in the central amygdaloid nucleus was not affected by this treatment but higher binding levels were found in the most caudal sections irrespective of hormonal status or sex. No sex differences were detected in OT binding in the VMN of basal or EB-treated animals. These results suggest that a dose of EB which activates female sexual behavior in female but not in male rats is able to induce similar levels of OT binding in the VMN of animals of both sexes.     

Postnatal development and sex differences in hepatic phosphatidate phosphohydrolase activity in the rat

The mechanism leading to the difference in hepatic triacylglycerol metabolism between female and male rats was investigated by studying the ontogeny of hepatic soluble phosphatidate phosphohydrolase activity in feeding animals of both sexes. A sevenfold increase occurred within 12 hr of birth, returning to the adult level during the third postnatal day. The changes in enzyme activity were followed by similar changes in hepatic triacylglycerol concentrations. A sex difference was observed only in the adult rats, where the enzyme activity in the livers of feeding female rats was about 25% higher than that in the feeding males. The effects of gonadectomy and sex steroids were studied in a separate series of experiments on fasting animals. The activity of the soluble enzyme was 65% higher in the intact female rats than in the males, and that of the microsomal enzyme 130% higher. The activity ratio between the soluble and microsomal enzyme in the male rats was 4.3 on a liver wet weight basis with the methods used. Gonadectomy increased the soluble and microsomal activities by 25% and 80% respectively within 6 wk in the male rats. The soluble and microsomal activities were still at the same control levels 2 wk after the gonadectomy, the subcutaneous implants of testosterone or estradiol resulting in 10-fold increases in plasma hormone levels had no effects on these enzyme activities, although testosterone caused 50% decrease in the hepatic triacylglycerol concentration. These data indicate that, if hormonally mediated, the postnatal increase in phosphatidate phosphohydrolase activities is not related to sex steroids and also suggest that the basis of the sex difference in hepatic soluble phosphatidate phosphohydrolase activity remains to be established.