Sex differences in adrenocortical structure and function. XIV. Heparin-releasable liver-lipase like activity in rat adrenals as affected by gonadectomy and testosterone or estradiol replacement

Heparin-releasable liver-lipase like activity was studied in adrenals of intact, gonadectomized and gonadectomized-testosterone or estradiol replaced rats. Besides acid lipase, rat adrenals contain a neutral lipase activity. From both male and female adrenals about 70% of this activity is extractable by heparin containing medium. Activity of this lipase in 8000 g supernatant was higher in female than male adrenals. Orchiectomy of 12 weeks duration increased neutral lipase activity in rat adrenal, an effect reversed to normal level by testosterone replacement. On the other hand ovariectomy had no effect while estradiol replacement resulted in an increased activity of the neutral lipase of rat adrenal gland. The results showed a distinct sex-difference in heparin-releasable liver-lipase like activity of rat adrenals which depends on the inhibitory action of testosterone on the enzyme activity.     

The effect of corticotrophin on liver-type lipase activity in adrenals, liver and high-density lipoprotein subfractions in the rat

Hypercortisolism was induced in rats by the administration of a corticotrophin analogue (Synacthen depot). The effect of this treatment during different periods was studied in normally fed and overnight-fasted rats. The activity of liver-type lipases, i.e., of lipases similar to the heparin-releasable lipase of rat liver (liver lipase), was determined in the adrenal gland and in the liver. Short-term (16 h) treatment had no effect on the lipase activity in the adrenal gland. During prolonged treatment, however, the lipase activity rose to 600-700% of control values in 10 days and from then on remained constant. The effect was similar in fed and overnight-fasted rats. The lipase activity in the liver decreased upon Synacthen administration. In the fed rats a decrease of 25% of the initial value was found after 16 h, 40% after 3 days and 50% after 20 days of treatment. In overnight-fasted rats the lowering of the lipase activity was less marked than in fasted controls. Serum lipid levels and high-density lipoprotein (HDL) subclass concentrations were also measured. The cholesterol concentration in the lipoproteins with a density greater than 1.050 g/ml (HDL) was elevated in rats treated for 3-20 days. If the rats were treated for longer than 10 days, overnight fasting led to a normalization of the HDL-cholesterol levels. After separation of the HDL into two subfractions, a relatively 'light' apolipoprotein E-rich fraction and a more 'heavy' apolipoprotein A-I-rich fraction, in fed and fasted animals treated with Synacthen for 3 days both HDL subfractions were elevated. After 10 days treatment only the apolipoprotein A-I-rich HDL fraction was still enhanced in both fed and fasted rats.     

Corticosteroidogenesis in the hypertrophic adrenal gland produced by betamethasone 17, 21-dipropionate in the rat fetus

Betamethasone 17, 21-dipropionate (BMDP), a potent glucocorticoid, produces adrenal hypertrophy in the rat fetus. The present study was performed to investigate the possible alterations of corticosteroidogenesis due to endogeneous substrates or exogenous pregnenolone in the incubation of homogenates of fetal hypertrophic adrenals caused by BMDP given to pregnant rats at day 19 of pregnancy.The corticosteroidal products and those levels per mg homogenate in an incubate of the hypertrophic adrenal homogenate did not differ from those of a normal adrenal. No accumulations of abnormal precursors or intermediates were found in the incubates of the hypertrophic adrenals. It is concluded from these findings that no qualitative alterations in the pathway of corticosteroidogenesis occurred in the hypertrophic adrenal glands caused by BMDP in the rat fetus. When the calculation was done per adrenal gland, the content of corticosterone in the incubate of the homogenate of the hypertrophic adrenal was remarkably higher than that found in a normal gland. This finding was compatible with the significant increase of the plasma corticosterone concentration in the fetuses with the adrenal hypertrophy caused by BMDP.     

Morphochemical study of brown adipose tissue during adrenal gland regeneration in the white rat

The interscapular brown adipose tissue in male, white Wistar rats in the 1,3,6,15,30, and 60th day of regeneration of adrenals after their enucleation weas investigated. The tissue slides were stained with H and E, with Masson's triple stain and with Sudan B. The activity of the following dehydrogenses was evaluated: Succinic dehydrogenase, delta 5,3 beta-hydroxysteroid dehydrogenase and the activity of the following enzymes; monoaminooxidase (MAO), Alkaline phosphatase (AlPh) and acid phosphatase (AcPh) was studied. Between the first ad 30th day of regeneration of adrenals morphochemical changes were observed; a great number of cells with eosinophylic cytoplasm appeared and with minute vacuols in their cytoplasm, the blood vessels became more numerous and enlarged and the activity of the enzymes tested was enhanced, instead sudanophilia was weaken and the reaction of corticosteriods significantly intensified. The changes observed may indicate on an enhanced hormonal activity. The brown adipose tissue may function as an endocrine gland which supports the regenerating adrenals of the white rat, enables survival and preservation of homeostasis during the insufficiency of the adrenal cortex after adrenal enucleation. The initiation of the endocrine activity of the brown adipose tissue in the course of regeneration of the adrenals proceeds probably without the direct participation of catecholamines originating from the adrenals.     

Distribution and colocalization of nitric oxide synthase and NADPH-diaphorase in adrenal gland of developing,adult and aging Sprague-Dawley rats

The distribution and colocalization of nitric oxide synthase and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase) was investigated in the adrenal gland of developing, adult and aging rats with the use of immunohistochemical and histochemical techniques. Nitric oxide synthase-immunoreactive neurons within the adrenal gland were found from the 20th day of gestation onwards. During early development the neurons were found as small clusters of smaller-size cells compared to those observed in the adult gland. Their number reached that of adult level by the 4th day after birth, and in the glands from aging rats a 28.6% increase was observed. Whilst no immunofluorescence was seen in chromaffin cells during early development, some cells from glands of aging rats showed nitric oxide synthase-immunoreactivity with varying intensity. The immunoreactive neurons from postnatal rat adrenals were also positive for NADPH-diaphorase, whilst those in prenatal rats were negative or lightly stained. Nitric oxide synthase-immunoreactive nerve fibres were present in all adrenal glands examined from the 16th day of gestation onwards. A considerable degree of variation in the distribution of immunoreactive fibres both in medulla and outer region of cortex at the different age groups was observed and described. Most, but not all, nitric oxide synthase-immunoreactive nerve fibres also showed NADPH-diaphorase staining.     

Influence of fasting and dopamine on the tissue catecholamines diurnal variations

To define the role of catecholamines (CA) in the metabolic adaptation to fasting we examined the effect of exogenous dopamine(DA) on heat production(HP) and CA content in the interscapular brown adipose tissue(IBAT) and adrenals of control-fed and 2-day fasted rats in the morning(M) and in the evening(E). DA stimulates HP in fed rats in the M by 45% but the thermogenic effect of this CA is markedly higher in the E. However, DA had no thermogenic effect in fasted rats. The tissue CA in fed rats fluctuates diurnally: in the IBAT noradrenaline(NA) was much higher in the E while adrenaline(A) in adrenals was lower. DA in fed rats did not change the adrenal A but reduced NA content both in the adrenals and in the IBAT all over the day. Fasting depleted A from adrenals but increased NA content both in the M and in the E. Unlike the adrenals in the IBAT fasting did not affect NA content. In the adrenal gland of fasted rats DA significantly increased the A content to the equal degree during the day, while this CA had no effect on NA content of the IBAT.     

The influence of age on the activity of the renin-angiotensin system in rats with adrenal-regeneration hypertension

In female rats aged 21 and 80 days, uninephroadrenalectomy with enucleation of the remaining adrenal was performed and 0.17 mol X l-1 saline offered as the only drinking fluid. The changes of plasma concentration of renin (PRC), and its substrate (RSC) and renal renin activity (RRA), considered as an indicator of the secretory activity of the regenerating adrenal were studied 5, 10, 20, 40 and 60 days after the adrenal enucleation to look for possible age differences related to the higher susceptibility of immature rats to the hypertensive influence of the regenerating adrenal. It has been found that: 1. In adrenal-enucleated rats the saline-induced decrease of RRA was delayed for a shorter time period in immature rats than in adult ones (5 vs. 10 days), during which blood pressure, saline consumption and RSC were lowered. The decrease of PRC was retarded in the older group only. 2. In rats with regenerating adrenals the PRC and RRA decrease was greater in animals subjected to enucleation of the remaining adrenal gland when immature, than in those operated when adult. At the end of the experiment this age difference disappeared. 3. The age difference in PRC and RRA suppression appeared during the period, when neither blood pressure nor saline consumption were higher in immature rats than in adult ones. 4. In rats with regenerating adrenals the renal mass was greater than in saline drinking controls. In the younger group, which in contrast to the adult one developed hypertension, this increase was greater and directly related to the blood pressure level from the 20th post-enucleation day onwards. It is being suggested that the changes of PRC, RRA and RSC observed up to the 10th post-enucleation day indicates relative adrenal insufficiency, the shorter duration of which in immature rats reflects their higher sensitivity to mineralocorticoids produced by the regenerating adrenal. This also manifests itself by greater PRC and RRA suppression in this age group. The haemodynamic results of the greater RRA suppression in the not yet fully developed kidneys of immature rats may facilitate the development of a "vicious circle" mechanism between blood pressure and hypertensive renal damage and thus contribute to the higher sensitivity to adrenal-regeneration hypertension.     

Synthesis of hepatic lipase in liver and extrahepatic tissues

Immunoprecipitations of hepatic lipase from pulse-labeled rat liver have demonstrated that hepatic lipase is synthesized in two distinct molecular weight forms, HL-I (Mr = 51,000) and HL-II (Mr = 53,000). Both forms are immunologically related to purified hepatic lipase, but not to lipoprotein lipase. HL-I and HL-II are also kinetically related and represent different stages of intracellular processing. Glycosidase experiments suggest that HL-I is the high mannose microsomal form of the mature, sialylated HL-II enzyme. Hepatic lipase activity was detected in liver and adrenal gland but was absent in brain, heart, kidney, testes, small intestine, lung, and spleen. The adrenal and liver lipase activities were inhibited in a similar dose-dependent manner by hepatic lipase antiserum. Immunoblot analysis of partially purified adrenal lipase showed an immunoreactive band co-migrating with HL-II at 53,000 daltons which was absent in a control blot treated with preimmune serum. Adrenal lipase and authentic hepatic lipase yielded similar peptide maps, confirming the presence of the lipase in adrenal gland. However, incorporation of L-[35S]methionine into immunoprecipitable hepatic lipase was not detected in this tissue. In addition, Northern blot analysis showed the presence of hepatic lipase mRNA in liver but not adrenal gland. The presence of hepatic lipase in adrenal gland in the absence of detectable synthesis or messenger suggests that hepatic lipase originates in liver and is transported to this extrahepatic site.     

Hypertension from compression and/or enucleation of the adrenal glands in the rat.

Previos studies have shown that compression of the adrenal glands is as effective as adrenal enucleation in causing hypertension in rats. Unilateral adrenal enucleation is ineffective, however, if a normal contralateral adrenal gland is present. The studies reported herein demonstrate that unilateral compression also fails to cause hypertension in the presence of a normal contralateral gland. When present singly, either enucleate or compressed adrenals cause hypertension; when either is present with a normal contralateral gland, the blood pressure is unaffected. When compressed or enucleate glands constitute the pair, in any combination, hypertension ensues. However, whereas an enucleate gland remains extremely atrophic in the presence of a normal gland, compressed glands attain a much larger size under this circumstance. Furthermore, a compressed gland is less inhibitory to the regeneration of a contralateral enucleate gland than is a normal adrenal. Whereas enucleate glands, whether bilateral or unilateral, are always smaller than normal glands, compressed adrenals may be enlarged. The hypertensogenic function of compressed adrenals is, like that of enucleate glands, suppressed by the presence of a normal gland. The growth response of compressed or enucleate glands, whether bilateral or single, appears to depend upon the degree of injury inflicted upon them. There is a considerable discrepancy in the size of individual members of a pair when one or both have been injured, that members of a normal pair do not exhibit.     

Changes in rat adrenal cyclic nucleotides during normal and neoplastic growth

In an attempt to correlate changes in cyclic nucleotide levels with in vivo growth of the rat adrenal gland we have measured adrenal cyclic AMP and cyclic GMP in normal, hyperplastic, and neoplastic rat adrenals. The first group of animals were subject to either unilateral adrenalectomy (ADX) or acute hypophysectomy 1 h prior to unilateral adrenalectomy (HADX). Cyclic nucleotides were measured in the contralateral adrenal post-operatively. In HADX rats cyclic GMP rose steadily throughout the 7 day study period, while ADX rats exhibited significant decreases in adrenal cyclic GMP. Cyclic AMP remained approximately 1.5 pm/mg tissue in HADX rats, while in ADX rats there was significant elevation of adrenal cyclic AMP at all time points. Cyclic GMP/cyclic AMP ratios remained constant in HADX animals; however, the growing adrenals of ADX animals exhibited depressed cyclic GMP/cyclic AMP ratios at all time periods.Adrenal hyperplasia was induced in a seond group of animals by a transplantable, corticotropin-secreting, pituitary tumor. Adrenals from age-matched animals served as controls. Adrenal cyclic AMP was significantly elevated in tumor-bearers at a time correspinding to the peak accumulation of adrenal weight, protein and DNA in these animals. In contrast, adrenal cyclic GMP in both tumor-beares and control animals fell steadily throughout the study period. Cyclic GMP/cyclic AMP ratios of control animals decreased from 2 to 3 weeks post-transplant remaining at the 3 week value during the period corresponding to rapid adrenal growth in tumor-bearers. The cyclic GMP/cyclic AMP ratio in the hyperplastic adrenals of tumor-bearers decreased steadily throughout their rapid growth period, suggesting a positive correlation between adrenal growth and depression of the cyclic GMP/cyclic AMP ratio.Cyclic nucleotide levels in neoplastic adrenals of rats bearing the transplantable adrenocortical carcinoma 494 were compared with cyclic nucleotides in normal rat adrenal glands. Cyclic AMP was not different in the two groups. However, the cyclic GMP content of neoplastic adrenals was significantly lower than that of normal adrenal tissue, causing a suppression of the cyclic GMP/cyclic AMP ratio in the neoplastic tissue. Thus, measurement of adrenal cyclic nucleotides in both hyperplastic and neoplastic rat adrenal glands suggests that adrenal growth in vivo may be characterized by a depression of the cyclic GMP/cyclic AMP ratio.     

Monoclonal antibodies against salt-resistant rat liver lipase. Cross-reactivity with lipases from rat adrenals and ovaries

To obtain monoclonal antibodies against rat salt-resistant liver lipase, mice were immunized with enzyme purified from heparin-containing rat liver perfusates. Hybridomas were screened for antibody production by means of an enzyme-linked immunosorbent assay (ELISA) and an immunoprecipitation assay. Five hybridoma cell lines secreting antibodies against rat liver lipase indicated as A, B, C, D and E, have been obtained. All antibodies possess gamma one (gamma 1) heavy chains and kappa (kappa) light chains. The antibodies precipitate salt-resistant lipase from rat post-heparin plasma, are positive in ELISA, inhibit liver lipase activity and bind monospecifically with the enzyme as shown by immunoblotting. The monoclonal antibodies showed no significant reactivity with human liver lipase. The salt-resistant lipases of rat adrenals and ovaries are also precipitated by the monoclonal antibodies directed against the liver enzyme. Therefore, the heparin-releasable lipases of the liver, adrenals and ovaries possess identical epitopes.     

Adrenocortical function in 4-APP treated rats: a coupled stereological and biochemical study

Adrenocortical function in 4-APP-induced (4-aminopyrazolo[3,4-d]pyrymidine) lipoprotein-deficient rats was studied in relation to quantitative morphologic changes in the gland. 4-APP treatment results in enlargement of the adrenal cortex and its zona fasciculata and reticularis cells. In enlarged livers, cholesterol and free fatty acid concentrations were similar to that of control rats, however a marked accumulation of triglycerides with a concomitant drop in hepatic delta 4-steroid hydrogenase activity was found. A profound drop in serum cholesterol in both, high and low density lipoproteins, as well as triglycerides and plasma corticosterone concentrations was accompanied by a marked lowering of cholesterol and corticosterone concentration in the adrenal gland. Corticosterone output by adrenal homogenates was higher in 4-APP treated rats than in control animals. Such a treatment did not change cholesterol side-chain cleavage, 11 beta-hydroxylase, 3 beta-ol dehydrogenase-isomerase, steroid 5 alpha-reductase and neutral lipase activities when expressing results per unit weight of tissue or protein. However, when calculating per adrenocortical cell, adenine analogue applied increased 11 beta-hydroxylase, steroid 5 alpha-reductase and neutral lipase activities. Thus, coupled biochemical and stereologic studies revealed a complex and multidirectional effect of 4-APP on the rat adrenal cortex. This effect may be caused by serum lipoprotein deficiency and by toxic and stressful action of the adenine analogue on the rat. Also a direct effect of 4-APP on rat adrenal cortex may not be excluded.     

Influence of pinealectomy on the mitotic activity of regenerating adrenal cortex in rats

There is some evidence that the pineal gland may influence the proliferation of both normal and neoplastic cells. The adrenal cortex has very high capacity for regeneration. Therefore, the effects of pinealectomy on the mitotic activity of regenerating adrenal cortex of rats were studied on the second, seventh and twelfth days following the enucleation of adrenals. Pinealectomy caused a significant decrease in the mitotic index of regenerating adrenal cortex after 2 and 12 days in comparison to sham operated controls.     

Disturbed ovarian morphology,oestrous cycling and fertility of high fat fed rats are linked to alterations of incretin receptor expression

Obesity is a major cause of infertility in females with a direct correlation between energy intake and reproductive dysfunction. To explore underlying mechanisms, disturbances in reproductive health and incretin/reproductive hormone receptor expression were studied in female Wistar rats fed a high-fat-diet for 20-weeks. Metabolic parameters and ovarian/adrenal gene expression were monitored along with estrous cycling and fertility upon mating. High-fat-feeding significantly increased body weight, plasma insulin and HOMA-IR, indicative of obesity and insulin resistance. Estrous cycles were prolonged compared to normal chow-fed rats, with 50 % having an average cycle length ≥ 7days. Reproductive outcomes revealed high-fat-diet reduced litter size by 48 %, with 16 % rats unable to achieve pregnancy. Furthermore, 80 % of the high-fat group took > 35 days to become pregnant compared to 33 % fed a normal-diet. Also, 35 % of pups born to high-fat-fed rats were eaten by mothers or born dead which was not observed with control rats. These changes were associated with downregulation of Amh, Npy2R and GcgR gene expression in ovaries with upregulation of InsR and Glp-1R genes. In adrenals, Glp-1R, GipR, Npy2R, InsR, GcgR, GshR and Esr-1 genes were upregulated. Histological analysis of high-fat-diet ovaries and adrenals revealed changes in morphology with significantly increased number of cysts and reduced adrenal capsule thickness. Circulating levels of insulin, testosterone and progesterone was significantly higher in high-fat group with reduced FSH levels in plasma. These data demonstrate that high-fat feeding disrupts female reproductive function and suggest important interactions between gut and reproductive hormones in ovaries and adrenals which merit further investigation.     

Monoamine oxidase activity in the hypothalamus and various other brain areas and in some endocrine glands of the rat during the estrus cycle

—The activity of monoamine oxidase (MAO, EC 1.4.3.4) was measured in the entire hypothalamus and different hypothalamic regions, in the amygdala, frontal and lateral cerebral cortex, in the pituitary, adrenals and genital organs of male rats and of female rats during the estrus cycle. Activity of MAO changed cyclically in the hypothalamus, amygdala, adrenals and ovaries. The highest levels in the hypothalamus occurred at 10 a.m. on the day of proestrus and during estrus. The lowest levels occurred at 6 p.m. on the day of proestrus, of metestrus and during diestrus. Cyclical variations similar to those found in the whole hypothalamus were also observed in anterior, posterior and lateral portions and the median eminence of the hypothalamus. Activity in the median eminence was greater than that of the whole hypothalamus or its various other portions. The amygdala exhibited less marked cyclical activity which followed the pattern of the hypothalamus by increasing at 10 a.m. and peaking at 3 p.m. on the day of proestrus. At the‘post-critical’period of proestrus, when the activity of MAO in the hypothalamus and amygdala decreased, the activity of MAO in the ovaries and adrenals rose. During the estrus cycle much lower levels of activity of MAO were demonstrated in other regions of the brain (frontal and lateral cerebral cortex), in the pituitary and in the uterus, none of which showed cyclical changes. The changes in activity of MAO in cerebral tissues, endocrine glands and genital organs have been discussed in relation to the probable participation of monoamines in the mechanism(s) of secretion of gonadotrophins by the hypothalamus.     

Serum 11-deoxycorticosterone levels in adrenal-regeneration hypertension under conditions of quiescence and stress.

A time course study to measure adrenal cortical function was undertaken for the period prior to the development of hypertension until the onset of hypertension in the adrenal-regeneration hypertension (ARH) model. Quiescent rat kills were used so that all adrenal cortical parameters investigated would reflect basal or resting levels for controls. Thus a more accurate determination of the differences between control and experimental animals could be made. A radioimmunoassay procedure for deoxycorticosterone was developed to measure this steroid in individual rat serum samples. Elevated serum deoxycorticosterone levels were observed in rats with regenerating adrenals when they were killed under quiescent conditions. This agreed with our recently reported in vitro finding of restoration of cholesterol side chain cleavage activity while 11beta-hydroxylase activity remained imparied 25 days after adrenal enucleation. When rats were killed after ether stress, deoxycorticosterone levels were elevated in both control rats and in rats with regenerating adrenals but the difference was not significant. In contrast, after ether stress serum corticosterone levels were lower in rats with regenerating adrenals than in controls. These studies, in conjunction with our previous in vitro findings, point to the importance of deoxycorticosterone in the pathogenesis of adrenal regeneration hypertension and help to explain the anomalous corticosteroid secretion rate data found in this experimental hypertension model.     

Hepatic lipase in the rat ovary. Ovaries cannot synthesize hepatic lipase but accumulate it from the circulation

Hepatic lipase is proposed to have a role in steroidogenesis through its involvement in the metabolism of high density lipoproteins. We examined the activity, synthesis, distribution, and uptake of this enzyme and assessed the content of its mRNA in luteinized ovaries. We found that during peak steroidogenesis, ovaries of pregnant mare's serum gonadotropin-human chorionic gonadotropin-treated immature rats contained heparin-releasable hepatic lipase-like activity which was neutralized in a dose-dependent manner by purified antibodies to hepatic lipase isolated from post-heparin perfusates of rat livers. Quantitative immunoelectron microscopy revealed that ovarian hepatic lipase occurred along endothelial cells and was 3-fold more abundant in blood vessels of corpora lutea than those of stroma. However, hepatic lipase was not synthesized by the ovary since radiolabeled enzyme was not immunoisolated from the medium of dispersed luteinized granulosa cells incubated with [35S]methionine whereas it was present in the medium of control cells (hepatocytes). Similarly, hepatic lipase mRNA was detectable in liver but not ovaries or kidneys by Northern or slot blot analyses or by the polymerase chain reaction. Finally, 125I-labeled hepatic lipase injected into tail veins was quickly cleared from the systemic circulation, accumulating in liver, ovaries, kidneys, and spleen. Subsequent heparin injection caused rapid reappearance of radioactivity in the bloodstream and a marked decline of radiolabel in liver and ovaries but a modest decrease of that in kidneys and none in spleen. Exogenous 125I-bovine serum albumin also accumulated in all four organs but was not displaced from liver or ovaries by subsequent administration of heparin. Taken together, these data suggest that steroidogenically active ovaries possess but do not synthesize hepatic lipase. Instead, hepatic lipase originating elsewhere, presumably in the liver, is accumulated from the circulation at heparin-sensitive sites in ovarian blood vessels.     

A correlated morphological and biochemical study on the rat adrenal steroidogenesis

The ultrastructural and biochemical alterations produced by an hypocholesterolemic drug, 17 alpha-ethinyl estradiol, on the rat adrenal cortex were studied. Male rats aged two months and with approximately 200 g in weight were injected subcutaneously with 10 mg/kg/day of ethinyl estradiol during 9 days; rats injected with 1 ml propylene glycol were used as controls. The animals were sacrificed on the 10th day, and the adrenals from some of them were processed for electron microscopy. The adrenals from the remaining rats were used for measurements of the glands cholesterol and corticosterone, which were also measured in the blood. In estradiol-treated rats the zona fasciculata cells exhibited numerous microvilli, increase in the size of mitochondria and decrease in the number of lipid droplets. The quantitative analysis showed a significant increase of the volumetric density of mitochondria and microvilli and a significant decrease of the lipid droplets in the treated rats, when compared with normal ones. In treated rats, the concentration of cholesterol and corticosterone in the gland and blood were significantly decreased. These data show that hypocholesterolemia produced by estradiol has a remarkable effect on adrenal steroidogenesis, depletes the pool of adrenal cholesteryl esters, and evidences the role of plasma cholesterol in the corticosteroidogenesis.     

Streptozotocin-Induced Diabetes Decreases Mammary Gland Lipoprotein Lipase Activity and Messenger Ribonucleic Acid in Pregnant and Nonpregnant Rats

Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity in adipose tissue and development of hypertriglyceridemia. To determine how a condition of severe insulin deficiency affects mammary gland LPL activity and mRNA expression during late pregnancy, streptozotocin (STZ) treated (40 mg/kg) and non-treated (control) virgin and 20 day pregnant rats were studied. In control rats, both LPL activity and mRNA were higher in pregnant than in virgin rats. When compared to control rats, STZ-treated rats, either pregnant or virgin, showed decreased LPL activity and mRNA content. Furthermore, mammary gland LPL activity was linearly correlated with mRNA content, and either variable was linearly correlated with plasma insulin levels. Thus, insulin deficiency impairs the expression of LPL in mammary glands, revealing the role of insulin as a modulator of the enzyme at the mRNA expression level.     

Studies on adrenal delta-aminolevulinic acid synthetase.

The presence of δ-aminolevulinic acid synthetase (EC 2.3.1.37) in rat and bovine adrenals has been demonstrated. When untreated animals are employed, the activity of δ-aminolevulinic acid synthetase in rat and bovine adrenal homogenates is comparable to the activity found in hepatic homogenates. Adrenal δ-aminolevulinic acid synthetase is localized in the mitochondrial fraction and appears to be refractory to induction by agents that induce the hepatic enzyme. Starvation of rats increased adrenal δ-aminolevulinic acid synthetase activity without altering the activity of the hepatic enzyme. Treatment of rats with adrenocorticotropin also dramatically increased adrenal δ-aminolevulinic acid synthetase activity. These results suggest that the adrenal enzyme may be controlled by factors that differ from those which regulate the activity of the hepatic enzyme.