Paired pineals in the developing quail (Coturnix coturnix japonica) embryos

Paired pineals were observed as an anomaly in embryonic quail brains between 7 and 9 days of incubation. The size of each pineal was almost the same as that of the normal pineal and it was located slightly lateral of the midline. Histological examination of these paired pineals revealed that both had similar cytological features in comparison with the normal pineal of the same developmental stage. No abnormal features were detected in brains and eyes of the embryos with paired pineals. Since the presumptive pineal rudiments are considered to exist in the neural folds and to fuse in the midline during the formation of the neural tube, the paired pineals may be interpreted as a result of incomplete fusion of the pineal anlagen. This report describes for the first time the symmetrical occurrence of pineal glands in the developing avian brain.     

Circadian melatonin and young-to-old pineal grafting postpone aging and maintain juvenile conditions of reproductive functions in mice and rats

Chronic, night administration of melatonin to aging mice and transplantation of a young pineal gland into the thymic rudiment of older mice and rats have been studied with the aim of evaluating their effects on aging of gonadal, sexual, and reproductive functions. Both melatonin administration and young-to-old pineal grafting positively affect size and function of testes and maintenance of juvenile hippocampal and testicular LHRH-receptors and beta-adrenergic receptors in the tests of old rats and mice. These results demonstrate that a pineal-directed circadian function and cyclicity is fundamental for the regulation of sexual, reproductive physiology, and that proper intervention with melatonin may potentially postpone aging of both neural and gonadal sexual function.     

The effects of pineal indoles given late in the light period on reproductive organs and pituitary prolactin levels in male golden hamsters

Intact and pinealectomized adult male hamsters kept in light:dark cycles of 14:10 (in hours) were given daily injections of either 25 microgram melatonin, 5-methoxytryptophol, N-acetylserotonin, or 6-hydroxymelatonin at 19.00 hours (13h after lights on). The injections were continued for 50 consecutive days. The daily melatonin injections significantly elevated body weights and depressed the growth of the testes and accessory sex organs and pituitary prolactin levels in intact hamsters. By comparison, in pinealectomized animals daily afternoon melatonin injections failed to alter body or testicular weights or pituitary prolactin levels. These findings indicate that for single injections of melatonin to be antigonadotrophic in the male hamster, the pineal must be intact. In intact animals, 5-methoxytryptophol and N-acetylserotonin slightly depressed the growth of the reproductive organs and pituitary prolactin levels, respectively. Again, these effects were negated by removal of the pineal gland. 6-Hydroxymelatonin was without influence on any of the parameters of reproduction that were measured.     

Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields

The purpose of these experiments was to determine whether the exposure of rats at night to pulsed DC magnetic fields (MF) would influence the nocturnal production and secretion of melatonin, as indicated by pineal N-acetyltransferase (NAT) activity (the rate limiting enzyme in melatonin production) and pineal and serum melatonin levels. By using a computer-driven exposure system, 15 experiments were conducted. MF exposure onset was always during the night, with the duration of exposure varying from 15 to 120 min. A variety of field strengths, ranging from 50 to 500 microT (0.5 to 5.0 G) were used with the bulk of the studies being conducted using a 100 microT (1.0 G) field. During the interval of DC MF exposure, the field was turned on and off at 1-s intervals with a rise/fall time constant of 5 ms. Because the studies were performed during the night, all procedures were carried out under weak red light (intensity of <5 microW/cm2). At the conclusion of each study, a blood sample and the pineal gland were collected for analysis of serum melatonin titers and pineal NAT and melatonin levels. The outcome of individual studies varied. Of the 23 cases in which pineal NAT activity, pineal melatonin, and serum melatonin levels were measured, the following results were obtained; in 5 cases (21.7%) pineal NAT activity was depressed, in 2 cases (8.7%) studies pineal melatonin levels were lowered, and in 10 cases (43.5%) serum melatonin concentrations were reduced. Never was there a measured rise in any of the end points that were considered in this study. The magnitudes of the reductions were not correlated with field strength (i.e., no dose-response relationships were apparent), and likewise the reductions could not be correlated with the season of the year (experiments conducted at 12-month intervals under identical exposure conditions yielded different results). Duration of exposure also seemed not to be a factor in the degree of melatonin suppression. The inconsistency of the results does not permit the conclusion that pineal melatonin production or release are routinely influenced by pulsed DC MF exposure. In the current series of studies, a suppression of serum melatonin sometimes occurred in the absence of any apparent change in the synthesis of this indoleamine within the pineal gland (no alteration in either pineal NAT activity or pineal melatonin levels). Because melatonin is a direct free radical scavenger, the drop in serum melatonin could theoretically be explained by an increased uptake of melatonin by tissues that were experiencing augmented levels of free radicals as a consequence of MF exposure. This hypothetical possibly requires additional experimental documentation.     

Effects of zinc on intact and castrated cockerels

1. Fourteen-week-old intact and castrated cockerels (White Leghorn) were injected intramuscularly with zinc (100 micrograms/kg body weight) as zinc ammonium sulphate solution once daily for 4 weeks and the effects on testes, pituitary and adrenal glands investigated histologically. 2. In intact cocks zinc decreased testes weight significantly, inhibited spermatogenesis and disturbed testicular hormone production. There was an increase in pituitary gonadotrophic cell activity, perhaps an indication of feed-back response to low concentration of testicular hormone. Cortical and medullary cells of the adrenal glands showed signs of activation. 3. No discernible effects of zinc injection on pituitary and adrenal cells of castrates were observed. This may reflect a decrease in pituitary and adrenal responsiveness to repeated stimulation with zinc. 4. The results indicate that the effectiveness of a given dose of zinc was dependent on the physiological condition of the cockerels and the effective site of zinc action was centred in the testes.     

The effect of dexamethasone administration at different stages of gestation on maternal plasma steroid concentrations in the baboon (Papio cynocephalus)

Dexamethasone administration at different stages of gestation in the baboon was studied for its effect on maternal steroid hormone concentrations. Dexamethasone (2 mg i.m. at 12 h intervals for three doses) was administered at early (days 37-39), mid (days 76-85) or late (days 112-123) gestation and morning blood samples were collected before, during and after dexamethasone suppression for 6 consecutive days. Dexamethasone treatment, at all stages of pregnancy, resulted in a significant decline in maternal serum cortisol concentrations, which rapidly return to normal concentrations after treatment. Progesterone concentrations were not affected by dexamethasone at any stage of gestation. Serum concentrations of oestradiol, testosterone and androstenedione were unchanged following dexamethasone administration in early pregnancy. A trend toward lower serum oestradiol was observed following dexamethasone administration in both mid and late gestation, but this was not significant. Both testosterone and androstenedione were significantly decreased following dexamethasone in both mid and late pregnancy and recovered to pretreatment concentrations within a few days after cessation of treatment. These results confirm other studies which demonstrate that adrenal precursors (maternal or fetal) are a major contributor to maternal serum concentrations of oestradiol. They also demonstrate that these adrenal precursors increase serum concentrations of testosterone and androstenedione in the pregnant baboon. Since these changes are only evident after that time (>40 days) when the fetal adrenal is steroidogenically competent, a role for fetal adrenal involvement in maternal serum androgen concentrations is suggested.     

Gonadotropins are essential modifier factors for gonadal tumor development in inhibin-deficient mice

We previously demonstrated that mice deficient in inhibin develop gonadal sex cord-stromal tumors with nearly 100% penetrance. These ovarian and testicular tumors develop as early as 4 weeks of age and eventually cause cachexia-like symptoms and death in the inhibin-deficient mice. Gonadectomized inhibin-deficient mice initially do not develop this wasting syndrome, but eventually will develop adrenal cortical tumors with similar penetrance. These studies have demonstrated that inhibin is a secreted type of tumor suppressor in the gonads and adrenal glands. Gonadotropins are implicated to influence gonadal tumor development in humans as well as experimental animals, and in inhibin-deficient mice, serum FSH levels are elevated. To determine whether gonadotropins influence the development and/or progression of the tumors in the inhibin-deficient mice, we took advantage of a naturally occurring mutant mouse, hypogonadal (hpg); hpg/hpg mice lack a functional GnRH gene and, therefore, have suppressed FSH and LH levels. Heterozygous hpg/+mice were crossed to heterozygous inhibin mutant mice to generate compound homozygous mutant mice that lack both inhibin and GnRH. These compound homozygous mutant mice do not develop a wasting syndrome, do not exhibit gonadal or adrenal tumors, and can survive for more than 1 yr. These results demonstrate that gonadotropins are essential modifier factors for tumor development in inhibin-deficient mice.     

Parietal eye-pineal morphology in lizards and its physiological implications

Pineal complexes in 85 species of lizards examined comprised seven morphological types. Members of the same family do not necessarily have the same pineal complex type. "Regressive" parietal eyes were not common except in certain arboreal lizards, primarily from the family Chameleontidae. The parietal eye is often retained in burrowing lizards, presumably because these animals are occasionally exposed to light and the parietal eye is a more suitable photoreceptor for a burrower than are lateral eyes. The pineal of certain lizards possesses a finger-like projection that extends toward the parietal eye. This extension, along with pineal wall convolutions, results in more photoreceptor cells oriented for maximal absorption of light. It is rare to find convolutions and an extension in the same pineal. Cartilage deposits and blood sinuses may modify the intensity and wavelength of light reaching the pineal. These observations suggest that the intracranial pineal of lizards is a more important photoreceptor than was previously realized, a situation that may be a factor in the occasional "failure" of parietalectomy experiments.     

Direct anti-atherosclerosis-related effects of garlic

Leydig cell tumors are very rarely seen testicular tumors and can be difficult to distinguish from testicular tumors of the adrenogenital syndrome. Testicular tumors of the adrenogenital syndrome are confined to patients with congenital adrenal hyperplasia. The authors report a case of a patient with malignant Leydig cell tumor and a history of congenital adrenal hyperplasia (adrenogenital syndrome). To the authors' knowledge, this has not been reported previously.     

Regulation of immunoreactive androgen receptor in the adrenal gland of the adult rat

The androgen receptor (AR) was measured by an immunoblot assay in adult tissues of both male and female rats. Relatively high levels of AR were detected in tissues of the male urogenital tract and in the adrenal glands and gonads of both sexes. Another group of tissues, including the male levator ani/bulbocavernosus muscles, preputial gland, scrotal skin, and vagina, had low, but detectable, levels of AR. In a third group of tissues, including the uterus, kidney, spleen, liver, gut, heart, lung, pituitary, and hypothalamus, AR was undetectable. In some androgen target tissues, such as the penis, androgens cause an apparent disappearance of AR from the tissue, and in other tissues, such as the ventral prostate, androgen therapy increases the amount of detectable AR. We compared the effect of androgen on AR levels in the adrenal gland and ventral prostate, tissues that differ markedly in their trophic responses to androgen. Castration appeared to have no effect on the amount of detectable AR in the adrenal gland, whereas it caused a profound decrease in AR levels in the ventral prostate. By contrast, 7 days after hypophysectomy, AR levels declined in both the adrenal gland and the ventral prostate. The effects of hypophysectomy plus castration were similar to those of hypophysectomy alone. Administration of ACTH to hypophysectomized rats for 7 days did not reverse the effects of hypophysectomy on adrenal AR, nor did treatment with levothyroxine, dexamethasone, rat GH, or rat PRL. Treatment of hypophysectomized rats with 5alpha-dihydrotestosterone for 7 days caused a dramatic increase in the amount of detectable AR in both the ventral prostate and the adrenal gland, but had a trophic effect only in the ventral prostate. These findings suggest that the amount of immunoreactive AR detected in both the adrenal gland and the ventral prostate is enhanced by androgens: testicular androgens in the case of the ventral prostate and adrenal androgen in the case of the adrenal glands.     

Ovine arylalkylamine N-acetyltransferase in the pineal and pituitary glands: differences in function and regulation

The enzyme arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) has been conventionally linked with the biosynthesis of melatonin within the pineal gland and retina. This study establishes that AANAT messenger RNA (mRNA) and functional enzyme occurs within the pars tuberalis (PT) and to a lesser degree within the pars distalis (PD) of the sheep pituitary gland; expression in these tissues is approximately 1/15th (PT) and 1/300th (PD) of that in the ovine pineal gland. AANAT mRNA in the PT appears to be expressed in the same cells as the Mel1a receptor. No evidence was obtained to indicate that either PT or PD cells have the ability to synthesize melatonin, suggesting that this enzyme plays a different functional role in the pituitary. We also found that cAMP regulation of the abundance of AANAT mRNA differs between the PT and pineal gland. Forskolin (10 microM) has no effect on pineal AANAT mRNA levels, yet represses expression in the PT. This suppressive influence could be mediated by ICER (inducible cAMP response early repressor), which is induced by forskolin in both tissues. Although it appears that the specific function and regulation of AANAT in the pituitary gland differ from that in the pineal gland, it seems likely that AANAT may play a role in the broader area of signal transduction through the biotransformation of amines.     

Role of androgens in testicular tumor development in inhibin-deficient mice

To understand gonadal tumor development, we have previously created a mouse model in which mice deficient in the inhibins develop gonadal sex cord-stromal tumors with essentially 100% penetrance. These tumors develop as early as 4 weeks of age and cause cancer cachexia-like symptoms and subsequent death in the inhibin-deficient mice. Gonadectomized inhibin-deficient mice eventually develop adrenal cortical tumors with nearly 100% penetrance. These studies have identified inhibin as a novel secreted tumor suppressor protein with specificity for the gonads and adrenal glands. Sex steroids have been implicated to influence gonadal tumor development in humans and mice. To determine the role of androgens in gonadal tumorigenesis in inhibin-deficient male mice, we have used a genetic intercross strategy, breeding inhibin alpha mutant mice with tfm (testicular feminization, a naturally occurring androgen receptor mutant) carrying females to eventually generate compound mutant male mice that lack inhibins and carry the tfm mutation. These compound mutant mice, like inhibin-deficient mice, continue to develop testicular tumors and the accompanying cancer cachexia-like wasting syndrome. Consistent with these findings, elevated levels of activins A and B secreted from the gonadal tumors are seen in the adult compound mutant mice as well as the secondary pathological consequences of these high activin levels in the livers and glandular stomachs. However, in contrast to male mice lacking only inhibin, in which essentially 100% of the testicular tumors are hemorrhagic, 65% of the tumors in these compound mutant male mice are less hemorrhagic, and approximately 50% of the compound mutants live longer than 17 weeks of age (95% of the male mice lacking only inhibin die by 12 weeks). These results suggest that androgens are not required for testicular tumor development in inhibin-deficient mice, but may play a regulatory role in testicular tumor progression.     

Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging

The present data show a dramatic decline in the circulating levels of dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), androst-5-ene-3 beta,17 beta-diol (5-diol), 5-diol-sulfate, 5-diol-fatty acid esters, and androstenedione in both men and women between the ages of 20-80 yr. In the 50- to 60-yr-old group, serum DHEA decreased by 74% and 70% from its peak values in 20- to 30-yr-old men and women, respectively. the serum concentrations of the conjugated metabolites of dihydrotestosterone (DHT), namely androsterone (ADT)-G, androstane-3 alpha,17 beta-diol (3 alpha-diol-G), androstane-3 beta,17 beta-diol (3 beta-diol-G), and ADT-sulfate are the most reliable parameters of the total androgen pool in both men and women, whereas serum testosterone and DHT can be used as markers of testicular secretion in men and interstitial ovarian secretion in women. The serum concentration of these various conjugated androgen metabolites decreased by 40.8% to 72.8% between the 20- to 30-yr-old and 70- to 80-yr-old age groups in men and women, respectively, thus suggesting a parallel decrease in the total androgen pool with age. As estimated by measurement of the circulating levels of these conjugated metabolites of DHT, it is noteworthy that women produce approximately 66% of the total androgens found in men. In women, most of these androgens originate from the transformation of DHEA and DHEA-S into testosterone and DHT in peripheral intracrine tissues, whereas in men the testes and DHEA and DHEA-S provide approximately equal amounts of androgens at the age of 50-60 yr. An additional potentially highly significant observation is that the majority of the marked decline in circulating adrenal C19 steroids and their resulting androgen metabolites takes place between the age groups of 20- to 30-yr olds and 50- to 60-yr-olds, with smaller changes are observed after the age of 60 yr.     

Adrenal function in the diabetic mutant mouse (gene symbol dbm)

The adrenal function in diabetes mutant mice with misty coat colour (dbm) was investigated by measurements of serum corticosteroids, adrenal weights and adrenal corticosteroid content. Furthermore, the adrenal corticosteroid content was studied in obese-hyperglycemic mice (ob). In the dbm-mice the serum corticosteroid levels were elevated at the age of 5 and 12 months although the adrenal weight only was significantly elevated at the age of 5 months. The adrenal corticosteroid content was significantly lower in the 12 months old dbm-mice. In the ob-mice the adrenal corticosteroid content was elevated at the age of 5 weeks, 5 and 12 months. It is concluded that in both the dbm-mouse and the ob-mouse there is an increased functional activity of the adrenal cortex which may reflect a pituitary hypersection of ACTH, perhaps as a manifestation of a common hypothalamic disorder.     

Identification of chaperonin particles in mammalian brain cytosol and of T-complex polypeptide 1 as one of their components

An approximately 950-kDa heteromeric particle was purified from guinea-pig and rat brain by sucrose gradient fractionation of post-mitochondrial supernatants. Further purification, by affinity chromatography on ATP-Sepharose and anion exchange FPLC on MonoQ, yielded a particle with typical chaperonin ultrastructure. One of the component polypeptides was recognized by a monoclonal antibody to murine T-complex polypeptide 1. Brain cytosolic chaperonin particles formed a binary complex with unfolded tubulin subunits. The polypeptide compositions of the cytosolic chaperonin particles appeared very similar between brain and testicular tissues of the same animal, but differed subtly between the guinea-pig and rat.     

Assessment of efficacy of pyridoxine in control of radiation induced sickness

A case of focal nodular hyperplasia (FNH) of the liver and an adrenal pseudocyst coexisting in the same patient is presented. The presentation was due to the large adrenal pseudocyst, which caused abdominal pain and swelling. At operation, the FNH was noted as an incidental finding. The aetiopathogenesis of both these lesions is thought to be the result of vascular malformation. FNH is associated with several other vascular malformations and lesions, and the association with an adrenal pseudocyst extends this concept. It also lends support to the theory that vascular abnormalities are important in the causation of these lesions.     

Determination of trace amounts of albumin in human bronchoalveolar lavage fluids by fluorometry with chromazurol S

Effects of altered gonadotropin and prolactin (PRL) secretion on luteinizing hormone (LH), PRL and their testicular receptors (R) were studied in neonatal and adult rats. Changes in gene expression were monitored by measurements of steady-state mRNA levels. Five-day and 90-day-old male rats received a single s.c. injection of hCG (600 IU/kg), 1 mg/kg bromocriptine (BR) twice daily, or their combination. After 2 or 8 days, the responses of LH, PRL, their testicular R, and testosterone (T) were assessed, including measurements of the appropriate mRNA levels. Vehicle-treated age-matched animals served as controls. hCG suppressed serum LH in 2 days in adult rats from 0.85 +/- 0.16 to 0.04 +/- 0.01 microg/l, and in neonates from 0.59 +/- 0.29 to levels below 0.01 microg/l (p < 0.01 for both). This was accompanied at both ages by a 60% decrease in pituitary content of the LH beta-subunit mRNA (p < 0.01), but a decrease in the alpha-chain (40%, p < 0.05) occurred only in neonates. hCG increased serum PRL in adult rats in 8 days over 2-fold (p < 0.01); this did not occur in neonates. In neonates, BR increased the LH subunit mRNAs 2-fold in 8 days (p < 0.01) without a concomitant effect on serum LH; no BR effects on the LH parameters were seen in adult animals. BR decreased pituitary PRL protein and mRNA levels at both ages (p < 0.01-0.05), but serum PRL decreased only in the adults. The homologous down-regulation of testicular LHR (near 100%) was accompanied in adults by a 30% decrease in LHR mRNA (p < 0.05). Also BR at this age decreased LHR binding (75% in 8 days, p < 0.01), but in this case no change occurred in the cognate mRNA. hCG and BR slightly up-regulated in adults PRLR binding, but only the 2-day effect of BR was accompanied by a 60% increase in PRLR mRNA (p < 0.05). In neonates, both hCG and BR increased testicular LHR and PRLR mRNA levels (p < 0.01-0.05). In adult animals, both hCG and BR suppressed testicular and serum T levels after 8 days (40-70%, p < 0.01-0.05); only BR was inhibitory to T by 8 days in the neonates (p < 0.05). In conclusion, the homologous and heterologous regulatory effects of hCG and BR on LH, PRL and their testicular R levels were only partly explained by changes in steady-state levels of the respective mRNAs. In general, the autoregulatory effects on LHR and PRLR appeared to affect steady-state levels of cognate mRNAs, whereas heteroregulation predominately involved changes at the protein level. The responses of the neonatal pituitary-gonadal axis to hCG and/or BR differed greatly from those observed in the adult, indicating that the mechanisms involved in these regulatory events in adult animals are a result of gradual postnatal development.     

The effect of cervical sympathectomy on the pituitary and pineal endocrine system

It was reported previously that continuous exposure to light in male rats increased serum luteinizing hormone (LH) and bilateral cervical sympathectomy inhibited such a change. In the present report, to examine the effect of cervical sympathectomy on the pineal endocrine function, 30 male rats were assigned to five groups. The control (C) group and the light (L) group underwent sham sympathectomy as well as sham pinealectomy. The sympathectomy (S) group underwent sympathectomy and sham pinealectomy. The pinealectomy (P) group and pinealectomy-melatonine (PM) group underwent sympathectomy and pinealectomy. The C group was kept under a normal circadian rhythm for 10 days, and the other groups were kept under continuous exposure to light for the same period. The PM group received subcutaneously 10 mg.kg-1 of melatonine every day. Serum LH levels were measured 10 days following these experiments. With regard to serum LH levels, the differences among C group, L group, and S group were similar to those previously reported. It was higher in P group (2.53 +/- 0.40 ng.ml-1) than in S group (1.58 +/- 0.61 ng.ml-1), and lower in PM group (2.08 +/- 0.31 ng.ml-1) than in P group. In conclusion, it is suggested that the endocrine activity of melatonine from the pineal gland plays an important role in the appearance of the effect of cervical sympathectomy.     

Characterization and partial purification of a substance in the pineal gland which inhibits cell multiplication in vitro

A substance which inhibits the in vitro multiplication of 3 cell strains, 37 RC, KB and NCTC clone 929, was characterized in the sheep pineal gland and partially purified using three successive chromatography techniques, respectively on Sephadex G-25, CM-cellulose and Biogel P 60 columns. The sheep cerebral cortex and liver also contain, but at much lower concentration than in the pineal, substance(s) that behave in different tests like the factor isolated from the pineal. The nature of the antimitotic substance from the pineal is as yet unknown. It is not destroyed by treatment with proteolytic enzymes, nor by boiling with 6 M HC1. It was established that it is different from the known antiblastic drugs such as Daunomycin and Methotrexate and from some active substances known to be present in the pineal, such as melatonin, secotonin and norepinephrine, which, in the same conditions, did not show any antimitotic activity. It was shown that when the concentration of the pineal factor in the culture medium was high enough (10 mug/ml), the inhibition of the KB cells multiplication was complete and irreversible. Microscopic examination of the treated cells showed that the morphological alteration was rapid (3--6 h) and deep, with shrinkage of both cytoplasm and nucleus, while with antiblastic drugs, morphological alteration proceeded slower (1--3 days) and appeared less pronounced.     

Indications for a central innervation of the bovine pineal gland with substance P-immunoreactive nerve fibers

An antiserum, raised in rabbits, against substance P was used in an immunohistochemical investigation of the bovine pineal gland. A moderate innervation of all parts of the bovine pineal gland with substance P-immunoreactive nerve fibers was demonstrated. The immunoreactive nerve fibers were located throughout the pineal gland, both perivascularly, intraparenchymally, and with few fibers in the pineal capsule. Within the habenular nucleus, a large number of substance substance P-immunoreactive perikarya were present. From these perikarya processes extended towards the pineal stalk and gland. Some substance P-immunoreactive nerve fibers were located in the stria medullaris and in the posterior commissure. The anatomical location of the substance P-immunoreactive nerve fibers in the pineal gland and stalk strongly indicates that, in this species, substance P-immunoreactive pinealopetal nerve fibers originate from perikarya in the brain, probably from the medial habenular nucleus.