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Biomedical subjects

A Bartke

Publications and source records attributed to A Bartke.

At least 19 recordsLinked to original sources

Substance P variations in the hypothalamus of golden hamsters at different stages of the estrous cycle.

The changes in substance P concentrations in the hypothalamus of female golden hamsters were studied at the different stages of the estrous cycle. Substance P levels in the hypothalamus of hamsters were highest during estrus and lowest during diestrus I and proestrus. The concentrations of substance P during diestrus II were not significantly different from those observed during estrus. These results show that substance P levels in the hypothalamus of female hamsters undergo significant changes during the estrous cycle.

Animals

Structural response of the hamster Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study.

Reproductively active hamsters were hypophysectomized and examined 6 or 20 days later in a combined morphometric and endocrine study of the Sertoli cell to determine 1) the morphological and endocrine effects of hypophysectomy of both short- and long-term duration, 2) if regression of Sertoli cells after hypophysectomy in a seasonal breeder resembles regression due to seasonal changes, and 3) if effects of hypophysectomy in a seasonal breeder are equivalent to the effects of hypophysectomy in a nonseasonal breeder. Six days after hypophysectomy, at a period when germ cell degeneration is first noted, there was a significant decrease in testis weight, interstitial space, tubule diameter and length, volume of seminiferous tubule, and tubular lumen. There were no significant changes in Sertoli cell nuclear and cytoplasmic volume although cell surface area was decreased significantly. Most organelles exhibited no significant change in volume or surface area except for secondary lysosomes which expectedly increased in volume as the result of phagocytosis of germinal cells. Thus at an early time period when functional changes in germ cells and Leydig cells are clearly evident (Russell et al. [1992] Endocrinology), the Sertoli cell shows minimal changes. Twenty days after hypophysectomy, the cell, nuclear and cytoplasmic volumes and surface area of the Sertoli cells, and volumes and surface areas of nearly all organelles were significantly decreased from values measured in normal and in short-term hypophysectomized hamsters. The exceptions were the total volumes of lipid which increased significantly and lysosomes which were similar to normal but significantly lower than short-term hypophysectomized animals. The long-term hypophysectomized hamster Sertoli cell, like that of the short-day hamster (Sinha Hikim et al. [1989b] Endocrinology, 125:1829-1843) is structurally regressed as a whole rather than exhibiting selective decreases in cellular and subcellular components. The size of the Sertoli cell in pituitary-intact, long- and short-term hypophysectomized animals showed positive and significant correlations with the volumes and surface areas of all its cytoplasmic organelles except the volume of lipid which showed a negative, significant correlation. Comparisons of long-term hypophysectomized hamsters (in long-day light exposure) and short-day exposed animals (Sinha Hikim et al. [1989b] (Endocrinology, 125:1829-1843) suggested that hypophysectomy, in general, resulted in similar, but slightly more severe regressive changes in the testis and germ cell population than those seen during seasonal regression.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Nuclear receptor sites for vitamin D-soltriol in midbrain and hindbrain of Siberian hamster (Phodopus sungorus) assessed by autoradiography.

Autoradiograms were prepared from midbrains and hindbrains of male and female Siberian hamsters (Phodopus sungorus), kept under short-day or long-day illumination, after injection of tritium-labeled 1,25-dihydroxycholecalciferol (vitamin D, soltriol). Concentration and retention of radioactivity was noted in nuclei of certain neurons, glial cells, and ependymal cells, and in choroid epithelium. Labeled neurons of varying intensity were found throughout the brainstem in distinct populations at characteristic topographical sites, which include cranial nerve motor nuclei, the nucleus (n.) reticularis tegmenti pontis, the caudoventral region of the n. raphe dorsalis, the n. trapezoides, the n. vestibularis lateralis and n. vestibularis superior, neurons in the various nuclei of the sensory trigeminus, accessory optic nuclei, scattered neurons in nuclei of the reticular formation, the n. ambiguus, certain cells in the area postrema, and many others. Glial cells with nuclear labeling, probably microglia, were scattered predominantly in or near myelinated nerve fascicles. The choroid epithelium showed strong nuclear labeling throughout the ventricle. Nuclear labeling of ependyma was variable and weak, mainly at ventral and lateral extensions (recesses) of the ventricle. The extensive presence of nuclear binding in select neural structures indicates that vitamin D exerts specific genomic effects on cell populations that are known to be involved in the regulation of motor, sensory, autonomic, neuroendocrine, metabolic, and immune functions. The results of these studies, in conjunction with those from other brain and peripheral tissues, recognize vitamin D-soltriol as a steroid hormone with a wide scope of hormone-specific target cells, similar to estrogen, androgen, and adrenal steroids, and which are topographically distinct and characteristic for its functions as the steroid hormone of sunlight.

Animals

Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes.

The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated by the use of labelled ovine prolactin) was increased 2-3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice.

Animals

Changes in lymphoid organs of Ames dwarf mice after treatment with growth hormone, prolactin or ectopic pituitary transplants.

This study was performed to obtain more insight into the roles of PRL and GH in the control of immune functions in hereditary dwarf mice characterized by severe immunodeficiency. Adult female Ames dwarf mice (df/df) were injected daily for 10 days with ovine PRL (oPRL), bovine GH (bGH), oPRL+bGH or were implanted with a normal pituitary under the kidney capsule for 5 days. Only the treatment with bGH resulted in significant increases in the gain of body weight, and in absolute and relative thymus and spleen weights. Treatment with oPRL alone did not affect body weight gain or thymus and spleen weights. Treatment with oPRL+bGH produced a significant increase in the gain of body weight and in absolute and relative spleen weight but these effects were smaller than those measured in dwarf mice treated with bGH alone. Only bGH therapy resulted in extensive recovery of the absolute number of lymphocytes in the thymus and spleen of dwarf mice, with the values in treated dwarf mice not significantly different from those found in normal non-dwarf females. However, when these values were corrected for body weight, both the splenic and the thymic indices exceeded the values found in normal mice. The absolute numbers of lymphocytes in the spleen were also increased by oPRL+bGH treatment, but did not reach the values found in normal mice; however, the splenic index exceeded the values found in normal animals. Surprisingly, the absolute and relative numbers of lymphocytes found in the thymus of dwarf mice under oPRL+bGH therapy were indistinguishable from those found in oPRL or vehicle treated dwarf mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Identification of somatogenic binding sites in liver microsomes from normal mice and transgenic mice expressing human growth hormone gene.

Somatogenic binding sites were detected and characterized in microsomal preparations from livers of normal mice and mice expressing metallothionein-I/hGH (mMT/hGH) hybrid gene, using 125I-labelled bovine or human GH, or a photoreactive derivative of hGH (125I-AP-hGH1). Specific binding of 125I-bGH was detected in liver microsomes from both normal and transgenic mice with an apparent Kd of 2 nM. 125I-hGH was partially displaced by bGH. 125I-AP-hGH1 was covalently bound to the microsomal preparations, and bGH prevented the formation of the 130 kDa species with no appreciable effect on 63 kDa and 70 kDa lactogenic complexes.

Animals

Down regulation of masked and unmasked insulin receptors in the liver of transgenic mice expressing bovine growth hormone gene.

The interaction of insulin with its receptor was studied in microsomes from livers of transgenic mice expressing the bovine growth hormone gene with mouse metallothionein-1 promoter (MT/bGH) and in their normal (non-transgenic) littermates. Specific binding of 125I-insulin was detected in hepatic microsomes from normal and transgenic mice with an apparent Kd of 8 and 200 nM, for high and low affinity sites, respectively. The transgenic MT/bGH mice had a marked hyperinsulinism without significant elevation of plasma glucose levels. Under identical conditions of preparation and incubation, microsomes from the transgenic male and female mice bound 39% and 34% less insulin than those from their litter mates. Scatchard's analysis indicates that this decrease in binding is due to a decrease in the number of receptor sites. In contrast to the marked decrease in insulin binding to unmasked receptors, the levels of masked (also called cryptic) insulin receptors were similar (or slightly increased) in transgenic mice microsomes as compared to those of their normal litter mates.

Animals

Effects of treatment of normal and hyperprolactinemic rats with cyclosporine in vivo on the release of gonadotropins and prolactin from their pituitaries in vitro.

Cyclosporine (CyA) is extremely useful as an immunosuppressant and it is believed that at least some of its actions are due to antagonizing PRL effects. To determine whether the reported ability of CyA to inhibit gonadotropin release can be modified by PRL, we have examined the effects of treatment of normal and hyperprolactinemic rats with CyA in vivo on the release of LH, FSH and PRL from their pituitaries in vitro. Hyperprolactinemia was induced by implantation of capsules containing diethylstilbestrol (DES) and the animals were examined while the capsules were still in place (DES-IN) or after they had been removed (DES-OUT). Treatment with CyA significantly reduced plasma LH levels in control DES-IN rats without reducing basal LH release from the pituitaries of these animals in vitro. In the DES-IN rats, CyA exposure in vivo did not modify plasma PRL levels, but reduced PRL release in vitro, and interfered with the inhibitory action of dopamine (DA) on PRL release. The effect of DA on gonadotropin release in vitro was modified by CyA treatment. Administration of CyA failed to antagonize the suppressive effects of hyperprolactinemia on plasma LH and FSH levels or on the basal rates of gonadotropin release by incubated pituitaries. We conclude that CyA can reduce PRL release but does not interfere with the actions of PRL on anterior pituitary function.

Animals

Acute effects of delta-9-tetrahydrocannabinol on dopaminergic activity in several rat brain areas.

In this work, we examined the acute effects of two doses of delta-9-tetrahydrocannabinol (THC) on several pre- and postsynaptic biochemical measures of dopaminergic activity in the striatum, limbic forebrain, and hypothalamic-anterior pituitary area of adult male rats. The exposure to a low dose of THC (0.5 mg/kg bw) decreased the number of striatal D2 dopaminergic binding sites, but did not affect their affinity. Treatment with a higher dose of THC was ineffective. In addition, both doses decreased the number of D1 dopaminergic binding sites in the limbic forebrain without changing their affinity. We did not find any changes in the dopamine (DA) or L-3,4-dihydroxyphenylacetic acid (DOPAC) content, or in the DOPAC/DA ratio, in either the striatum or limbic forebrain. THC treatment produced a dose-related decline in plasma prolactin (PRL) levels. Furthermore, both the basal and DA-inhibited in vitro release of PRL were reduced in animals exposed to THC in a dose-dependent manner. This inhibitory effect of THC on PRL release was accompanied by a decreased DOPAC/DA ratio in medial basal hypothalamus that, in turn, may be a result of the fall in PRL levels rather than a direct action of the drug. These data show that acute exposure to THC can alter brain dopaminergic neurotransmission. Our results suggest that the reduction of PRL release following THC exposure, both in vivo and in vitro, might be elicited by a direct action of THC on the pituitary.

3,4-Dihydroxyphenylacetic Acid

Evaluation of the co-mutagenicity of ethanol and delta 9-tetrahydrocannabinol with Trenimon.

The mutagenic potential of chronic treatments of male CF-1 mice with ethanol and delta 9-tetrahydrocannibinol (THC), and their comutagenic potential with a known mutagenic agent, Trenimon, were examined. This was accomplished by measuring the frequency of dominant lethal mutations arising from mating of treated males with nontreated females. Adult male mice were treated with 5% (v/v) ethanol as part of a liquid diet (28% ethanol-derived calories) for five weeks; 10 mg/kg body weight (p.o.) THC every two days for five weeks; a single injection of Trenimon (0.125 mg/kg, i.p.) on day 28 of diet treatment; and all combinations of treatments. The control group was pair-fed a liquid diet in which isocaloric sucrose replaced ethanol; these males were also given sesame oil (vehicle for THC) and saline (vehicle for Trenimon) on the same schedule as that for the treated males. Neither body weights nor hematocrits were adversely affected by any treatment. Both ethanol and Trenimon treatments resulted in a small (8-9%; p less than 0.05) decrease in testicular weight. The effect of combined treatment with ethanol and Trenimon was roughly additive. Treatment with THC had no effect on testicular weight. Seminal vesicle weights were not affected by any treatment. Treatments were without significant effect on fertility, as measured by the frequency of males producing pregnancies. Ethanol and Trenimon treatments produced approximately 3- and 7-fold increases, respectively in the frequencies of preimplantational loss over that seen for the control group (7.3%), resulting in significant ethanol and Trenimon effects (p less than 0.001). No interactive effects of ethanol and Trenimon treatments were noted. Frequencies of dead fetuses per pregnancy in the ethanol- and Trenimon-treated groups were increased approximately 2.5- and 4-fold, respectively, over the control value of approximately 16%. However, the effect of combined treatments was not greater than that due to Trenimon alone, resulting in Trenimon and ethanol effects (p less than 0.001) and ethanol-Trenimon interaction (p less than 0.001). The calculated mutation index resulting from each treatment yielded significant (p less than 0.001) ethanol- and Trenimon-induced effects. In contrast to effects of ethanol and Trenimon treatments, THC, given alone, or in combination with ethanol and/or Trenimon, had no effect on either preimplantational loss, fetal mortality or the resulting mutation index. The data suggest that chronic ethanol treatment, at levels resulting in minimal fertility impairment, increases the frequency of dominant lethal mutations. In contrast, chronic treatment with THC, as administered in the present study, appears to be without effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance

Vitamin D nuclear binding to neurons of the septal, substriatal and amygdaloid area in the Siberian hamster (Phodopus sungorus) brain.

Autoradiographic experiments were performed on brains of Siberian hamsters (Phodopus sungorus) injected with tritiated 1,25-dihydroxycholecalciferol. Nuclear labeling was prevented in the presence of excess unlabeled hormone. Strong nuclear concentration of radioactivity was observed in neurons of the nucleus basalis of Meynert, the medial septal nucleus, the nucleus of the diagonal band of Broca and the central amygdaloid group. The latter has been defined as consisting of the central nucleus of the amygdala, its extension into the sublenticular part of the substantia innominata of Reichert, and the lateral division of the bed nucleus of the stria terminalis. All these structures have been reported to be involved in memory and other cognitive processes, and to be affected by age-dependent neurodegenerative disorders such as Alzheimer's disease. Corresponding localization of 1,25-dihydroxycholecalciferol receptor sites in these select basal forebrain nuclei of the Siberian hamster may implicate vitamin D (soltriol), the steroid hormone of sunlight, in memory processing.

Amygdala

Further observations on estrus and ovulation in woodchucks (Marmota monax) in captivity.

The woodchuck is a seasonally breeding sciurid rodent. Female woodchucks are monoestrous and, when isolated from males, remain in a prolonged period of estrus characterized by a clear predominance of cornified cells in the vaginal smear. This study was designed to characterize relationships between the degree of vaginal cornification and sexual receptivity, and to study ovulation and related phenomena of this species in captivity. Fourteen individually caged adult females, maintained under standard laboratory conditions for 9-23 mo, were used in this investigation. Females exhibiting predominantly (67-97%) cornified smears were always receptive, regardless of the time interval from the onset of estrus, and mated within 24 h of pairing. Mated females allowed to complete pregnancy gave birth to live pups 30-32 days later. Litter size ranged from 3-7 pups. Serum progesterone (P) levels increased to approximately 2 ng/ml during the first week of pregnancy and greater than 5 ng/ml during the second and third weeks of pregnancy. Serum estradiol (E2) levels were elevated during the first week of pregnancy and began to decline thereafter. Examination of ovarian serial sections revealed that ovulation took place between 20 and 32 h after copulation. Serum levels increased significantly (4-fold) after ovulation (1.2 +/- 0.3 vs. 0.3 +/- 0.01 ng/ml). However, the circulating levels of E2 remained unchanged between the periods before (53 +/- 1 pg/ml) and after ovulation (60 +/- 3 pg/ml). Ovulation was not simultaneous in all mature follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The influence of beta-endorphin on testicular endocrine function in adult rats.

The role of beta-endorphin in testicular steroidogenesis is poorly understood. To address this issue, we treated adult hypophysectomized rats intratesticularly with either saline-50% polyvinylpyrrolidone (SAL-PVP) or human beta-endorphin (0.5 microgram/testis; a total of 1 microgram/rat/day) in SAL-PVP for 3 days. Testicular injections were made under ether anesthesia. On Day 3, rats also received injections (s.c.) of either SAL-PVP or 5 micrograms beta-endorphin in SAL-PVP to minimize the dilution of ether in the testis. One hour later, rats were treated (i.p.) with either saline or ovine LH (25 micrograms/rat). One hour after saline or LH injection, blood was obtained via heart puncture for determination of plasma progesterone (P), androstenedione (A-dione), and testosterone (T) levels. The effects of beta-endorphin (50 ng, equivalent to 13.9 pM; or 250 ng, equivalent to 69.6 pM) on P and androgen secretions in vitro were also examined. Intratesticular injections of beta-endorphin significantly (p less than 0.025) decreased the T response to LH treatment, but failed to affect plasma P and A-dione levels. Response of P to LH treatment was increased (p less than 0.005) in medium containing testicular fragments exposed to 250 ng (69.6 pM) beta-endorphin. However, beta-endorphin attenuated LH effects on A-dione and T production in vitro. These studies demonstrate that beta-endorphin inhibits T secretion, possibly because of its effect on the synthesis of T precursors. Thus, testicular beta-endorphin modulates the endocrine function of the testis in adult rats.

Androgens

Isolation and culture of testicular macrophages from a seasonally breeding species, Phodopus sungorus. Evidence for functional differences between macrophages from active and regressed testes.

We have developed an isolation and cultivation protocol for testicular macrophages from the seasonally breeding Siberian hamster, Phodopus sungorus which allows serum-free culture. Macrophages were isolated from the active testes of adult Phodopus kept in long photoperiod (LD, 18hL:6hD), and from the inactive testes of animals with gonadal regression induced by exposure to a short photoperiod (SD, 6hL;18hD; for 10 weeks). The isolated cells were identified as macrophages by (a) electron microscopy, (b) non-specific phagocytosis, and (c) the presence of Fc-receptors. Treatment of the cultures with oFSH (at 0.5 and 1 micrograms ml-1 for 1 and 4 days) significantly stimulated lactate secretion by testicular macrophages from LD hamsters, as expected from studies in the rat. In marked contrast, oFSH did not affect lactate secretion by testicular macrophages from SD hamsters, or by peritoneal macrophages. To test possible macrophage-Leydig cell interactions, the influence of testicular macrophage-conditioned medium (TM-CM) from FSH-responsive LD macrophage cultures was assessed and compared with the effect of peritoneal macrophage-conditioned medium (PM-CM) on testosterone production by testicular parenchyma from LD hamsters. Unexpectedly, and in contrast to previous reports in rats, testosterone production by testes was inhibited significantly by TM-CM from cultures pretreated with either 0.1 or 0.5 micrograms FSH ml-1. FSH alone stimulated testosterone production (due either to LH contamination or to possible paracrine effects). PM-CM from cultures pretreated with FSH did have an inhibitory effect. It is concluded that: (i) There is indirect evidence for the presence of functional FSH receptors on macrophages from the active testes of Phodopus. (ii) Testicular macrophages from inactive testes of Phodopus are not responsive to FSH, implicating impaired macrophage function in the regressed testes of Phodopus exposed to SD. (iii) Testicular macrophages produce a factor which can inhibit testosterone production by incubated testicular tissue.

Animals

Neuroendocrine function in adult female transgenic mice expressing the human growth hormone gene.

Adult female transgenic mice expressing the human GH (hGH) gene with mouse metallothionein-I promoter are sterile. To evaluate the hypothalamic-pituitary function in these animals, adult female transgenic mice and nontransgenic normal littermates were ovariectomized. On days 7 and 8 after ovariectomy, mice were injected with either oil or primed with 0.5 micrograms estradiol benzoate (EB) in oil, 24 h later treated with 10 micrograms EB/100 g body wt and a day later bled for measurements of FSH, LH, and PRL levels. Plasma gonadotropin and PRL levels were also measured in ovary-intact transgenic and normal siblings at estrus. Additional ovariectomized EB-treated transgenic mice and normal siblings were injected with either saline or GnRH in saline (1 ng/g body wt) and were bled 15 min later for determination of circulating hormone levels. At estrus, in transgenic mice, circulating FSH and PRL levels were significantly lower (FSH:P less than 0.001; PRL:P less than 0.025), but plasma LH concentrations were higher (P less than 0.001) than those in nontransgenic mice. As expected, ovariectomy significantly increased (P less than 0.001) circulating FSH and LH levels in both groups of mice relative to ovary-intact animals, but the increase in plasma LH levels was attenuated in transgenic mice. The suppressive effect of estrogen on circulating FSH and LH levels were similar in transgenic and nontransgenic mice. Treatment with GnRH significantly increased plasma FSH and LH levels in both transgenic and normal mice. However, the plasma FSH and LH responses to GnRH administration were significantly reduced (P less than 0.001) in transgenic mice. The results of these studies indicate that adult female transgenic mice expressing the hGH gene are hypoprolactinemic. Yet due to PRL-like activity of hGH, the gonadotropin secretion is altered. Thus, endogenously secreted hGH modulates the hypothalamic-pituitary function of adult female transgenic mice bearing the hGH gene.

Animals

Structural manifestations of the rat Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study.

Although the Sertoli cell is a key cell mediating the actions of FSH- and LH-stimulated testosterone (T) in the testis, there is little information to indicate how this cell responds structurally to hormonal insufficiency. The present study used morphometric techniques to study the structural manifestations of the Sertoli cell in adult rats hypophysectomized for 6 and 28 days. Six days posthypophysectomy, a period when germ cell degeneration is first evident, tubular diameter and length, testis weights, volume of the interstitium, and volume of most parameters that comprise the interstitium (except blood vessels) showed significant regressive features. However, virtually no parameter relating to the volume and surface area of the Sertoli cell or its subcellular components was significantly reduced compared with that in the normal animal. Thus, at a time when germ cell degeneration is seen in the testis, the Sertoli cell showed no significant structural response to the changing endocrine status of the animal. In contrast, 28 days after hypophysectomy, virtually all parameters relating to the Sertoli cell and its organelles were significantly decreased compared with those in normal animals. Plasma and tissue testosterone, PRL, and FSH showed a very significant decrease 6 days after hypophysectomy compared with intact animals, but at 28 days there was no further significant decrease in the levels of these hormones. There was no correlation of most organelle volumes and surface areas with endocrine parameters. The size of the Sertoli cell showed positive and significant correlations with the volumes and surface areas of all of its cytoplasmic organelles, except the lipid volume. Short term hypophysectomy resulted in no significant change in either the concentration (femtomoles per mg protein) or the content (femtomoles per testis) of FSH receptors, nor was there a significant change in the number of FSH receptors per cell. However, 28 days after hypophysectomy only the content, not the concentration, of FSH receptors decreased significantly along with a decrease in the number of FSH receptors per cell. Although the marked degenerative changes that are seen in the testis 6 days after hypophysectomy parallel endocrine decline, the Sertoli cell responded slowly from a structural standpoint compared with the Leydig cell. After long term hypophysectomy, significant morphometric changes were observed in all of its structural parameters.

Animals

Structural changes in rat Leydig cells posthypophysectomy: a morphometric and endocrine study.

Short and long term responses of the rat Leydig cell were studied posthypophysectomy, at times when germ cell degeneration was first prominent (6 days) and after long term regression of the testis (28 days). In the short term, virtually all structural parameters relating to the volume and surface area of the Leydig cell and its subcellular organelles were significantly lowered compared with those in control animals. Exceptions were the volumes of the nucleolus, heterochromatin, and lysosomes and the surface areas of the nucleus. Structural decreases were generally on the order of 2- to 5-fold in the 6-day period. A statistical analysis of the percent decreases in the short term was performed to determine whether any particular structural features were more sensitive to hypophysectomy than any others. In most instances, no particular organelles were decreased compared to others. However, lipid, although not commonly seen in rat Leydig cells, showed significantly greater percent decreases compared with several other organelles, indicating that the small amount of lipid present is rapidly lost (used) in the short term. After long term hypophysectomy, all structural parameters of the Leydig cell were significantly lowered compared with those in pituitary-intact animals. Only a few parameters (mitochondrial volume, cell surface area, and the surface areas of inner and outer mitochondrial membranes and smooth endoplasmic reticulum) showed more significant decreases in the long term compared with the short term hypophysectomized animals. Most organelle volumes and surface areas correlated positively and significantly with serum and tissue testosterone levels; the exceptions were the volumes of the nucleolus, heterochromatin, lipid, and lysosomes. Compared with the pituitary-intact animal, the content of LH receptors expressed per testis and per Leydig cell was significantly lower in both hypophysectomized groups; however, the number of receptors per given area of individual Leydig cell plasma membrane remained unchanged. Overall, data show that the Leydig cell manifests marked structural changes during early spermatogenic dysfunction.

Animals

Transgenic female mice with high human growth hormone levels are fertile and capable of normal lactation without having been pregnant.

Transgenic mice carrying the phosphoenolpyruvate carboxykinase promoter region-human growth hormone (PEPCK-hGH) fusion gene are characterized by accelerated growth and plasma hGH levels ranging from 100 to 700 ng/ml. Both sexes are fertile, in contrast to previous findings in metallothionein-I/hGH transgenic mice in which females are sterile, apparently due to luteal failure. Virgin transgenic PEPCK/hGH females from this line produce milk and can successfully raise foster litters to weaning. We conclude that the life-long presence of very large amounts of hGH in the circulation is compatible with ovulation, can override the effects of hGH-induced suppression of endogenous PRL release, and can support full lactation in animals that have not been primed by hormonal changes associated with pregnancy.

Animals