Effect Of Hypophysectomy Research Articles

Effect of Hypophysectomy on Blood Coagulation and Fibrinolysis in Rats

Effect of Hypophysectomy on Blood Coagulation and Fibrinolysis in Rats

Immunolocalization of glutathione-reductase (GSSG-RD) in the rat adrenal cortex. Effect of hypophysectomy and ACTH administration.

Immunocytochemical localization of glutathione-reductase (GSSG-RD) in rat adrenal glands was studied in 1) normal untreated, 2) hypophysectomized, and 3) ACTH administered groups in order to clarify the biological significance of GSSG-RD in the adrenal cortical lipid metabolism including steroidogenesis. In the normal untreated group, GSSG-RD was immunohistochemically localized in all three zones of the adrenal cortex. In immunoelectron microscopic investigations, GSSG-RD was observed mainly in mitochondria. The hypophysectomized group showed atrophy of the zonae fasciculata and reticularis. GSSG-RD staining of the atrophic cortical zones was weakened. In immunoelectron microscopic investigations, GSSG-RD was observed not only in mitochondria but also in cytoplasmic matrix. On ACTH administration, the adrenal cortex became markedly hypertrophic, especially in the outer fasciculata. Immunohistochemically, GSSG-RD was mainly localized in the cells of those hypertrophic cortical zones. In immunoelectron microscopic investigations, GSSG-RD was observed not only in mitochondria but also in cytoplasmic matrix. These staining patterns were similar to those of glutathione-peroxidase (GSH-PO). GSH-PO reduces the lipid peroxides with concomitant oxidation of glutathione. Oxidized glutathione is reduced by GSSG-RD under the presence of NADPH. These two enzymes are known to be key enzymes of the lipid peroxides scavenging system. Based on our findings, it is strongly suggested that a very close relationship lies between the adrenal cortical GSSG-RD and steroidogenesis.

Thyroid Hormone Rapidly Induces Hepatic LDL Receptor mRNA Levels in Hypophysectomized Rats

The effects of hypophysectomy and thyroid hormone treatment on the expression of the hepatic LDL receptor gene was studied in young male rats. Hypophysectomy lowered levels of LDL receptor mRNA and protein. It was found that increased levels of LDL receptor mRNA could be detected 30 min after giving hypophysectomized rats an intramuscular injection of 10 μg of L-triiodothyronine (T3) per 100 g of body weight. This dose of T3 also increased hepatic LDL receptor protein levels within 1 h. A T3 dose of only 0.25 μg per 100 g increased LDL receptor mRNA levels more than threefold. The half-life of the hepatic LDL receptor mRNA was found to be about 30 min and was unaffected by T3. The data suggests that thyroid hormone acts physiologically to induce hepatic LDL receptor expression. This action may explain, in part, the hypocholesterolemic effect of the hormone.

Immunohistochemical analysis of EGF in epiphyseal growth plate from normal, hypophysectomized, and growth hormone-treated hypophysectomized rats

Epiphyseal growth plate cartilages from the proximal tibia of normal, hypophysectomized, and growth hormone (GH)-treated hypophysectomized rats were subjected to immunohistochemistry for detection of epidermal growth factor (EGF). In the normal growth plate, EGF was distributed mainly in the proliferative zone. Hypophysectomy resulted in considerable atrophy of the chondrocytes and the cartilage matrix (a decreased number of mature-type chondrocytes and a decreased ratio of proliferating to hypertrophic chondrocytes) and a significant diminution of EGF immunoreactivity. Treatment with GH reversed these effects of hypophysectomy, causing an increased thickness of the growth plate and EGF-reactive sites in all chondrocyte layers. The most intense immunostaining for EGF, however, was frequently seen in the nuclei of chondrocytes with flattened appearance. It appears that EGF could be incorporated or synthesized in chondrocytes having marked mitogenic activity. The present results, taken with previous data on EGF involvement in growth of cartilaginous tissue in vivo and in vitro, strongly suggest that EGF-immunoreactive chondrocytes are involved in cartilage proliferation and growth under the specific influence of GH.

Effect of Hypophysectomy on Corticotropin-Releasing Hormone and Adrenocorticotropin Immunoreactivities in the Rat Adrenal Gland

It has previously been shown that rat adrenal zona medullaris possesses an interleukin-1β (IL-1β)-responsive peripheral branch of the CRH/ACTH system that duplicates the hypothalamopituitary central one (Mazzocchi et al., Mol Cell. Neurosci. 4:267, 1993). The intraadrenal content of corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) immunoreactivities (ir), as well as IL-1β-stimulated release of CRH-ir and ACTH-ir, increased in relation to the number of days elapsed from hypophysectomy; the effect of hypophysectomy required at least 48 h to become significant and reached its maximum after 72 h. The action of IL-1β on ACTH-ir release was annulled by simultaneous exposure to α-helical-CRH, an antagonist of CRH. ACTH infusion, at a rate restoring a normal blood level of the hormone, prevented the effect of hypophysectomy on intraadrenal concentrations of both CRH-ir and ACTH-ir; similarly, the hypophysectomy-evoked rise in intraadrenal ACTH-ir content was completely annulled by treating hypophysectomized rats with CRH or dexamethasone. Taken together our findings suggest that the elimination of the central branch of CRH/ACTH system induces a marked increase in the activity of the intraadrenal peripheral one. The hypothesis is advanced that the hypophysectomy-induced lowering of circulating ACTH and the consequent drop in the production of adrenal glucocorticoids enhances, via a classic negative feedback mechanism, gene expression of CRH and ACTH in adrenal medullary chromaffin cells.

Effects of Hypophysectomy on Coho Salmon Interrenal: Maintenance of Steroidogenic Pathway and Restoration of in Vitro Responsiveness to Adrenocorticotropin after Handling

The role of the pituitary in regulating interrenal activity in coho salmon ( Oncorhynchus kisutch) was examined using short- (1 week) or long- (10 week) term hypophysectomized (Hx) animals. In experiments in which Hx animals were injected with ovine growth hormone (oGH), triiodothyronine, or vehicle, plasma cortisol was significantly lower (close to nondetectable, 1 ng/ml) in vehicle-injected or hormone-treated short- and long-term Hx animals compared to vehicle-treated sham-operated (SO animals). Treatment of long-term Hx animals with oGH led to a significant increase in plasma cortisol, in comparison to other Hx groups. Interrenal responsiveness to ACTH or cAMP was not consistently affected by hypophysectomy or hormone treatment. Pregnenolone-supported cortisol production by tissue from Hx groups was at least as great as that by tissue from SO animals: production by tissue from GH-treated, long-term Hx animals was significantly greater than that by tissue from Hx or SO animals. Similar experiments utilizing handling stress (handling and anesthesia) instead of hormone injection as a variable revealed that the response of tissue from Hx animals to ACTH or cAMP was significantly reduced in the absence of handling in comparison with SO animals. However, utilization of pregnenolone as a substrate by tissue from Hx animals was no different from that by tissue from SO animals and was independent of handling. These results indicate that the maintenance of the steroid-biosynthetic pathway is pituitary independent. The decrease in tissue responsiveness to ACTH or cAMP in undisturbed Hx animals may be partially attributable to: (1) the absence of nonpituitary/ nonpituitary-mediated factors that are stimulated by handling and which probably upregulate ACTH receptors and mediating systems; and/or (2) to the presence of inhibitory factors which are decreased after handling.

Effect of hypophysectomy on plasma catecholamines and enkephalins in fetal sheep.

The aim of this study was to determine the effect of fetal hypophysectomy on the plasma concentrations of catecholamines and enkephalins in the fetal sheep between 120 and 140 days gestation under basal and hypoxic conditions. During basal conditions, there was no difference in the plasma concentrations of norepinephrine and epinephrine between intact and hypophysectomized groups. Fetal plasma norepinephrine concentrations were significantly increased during hypoxia in intact fetal sheep (7.2 +/- 2.2 pmol/ml, -15 min; 20.2 +/- 7.7 pmol/ml, 30 min) between 130 and 140 days, but after fetal hypophysectomy there was no significant norepinephrine response to hypoxia at this gestational age (4.7 +/- 1.3 pmol/ml, -15 min; 8.8 +/- 2.8 pmol/ml, 30 min). In contrast, fetal plasma epinephrine concentrations were significantly increased during hypoxia in both the intact (1.5 +/- 0.5 pmol/ml, -15 min; 3.3 +/- 1.7 pmol/ml, 30 min) and hypophysectomized groups (1.8 +/- 0.6 pmol/ml, -15 min; 6.8 +/- 4.1 pmol/ml, 30 min) between 130 and 140 days. During basal conditions, plasma concentrations of free Met-Enk were significantly less in hypophysectomized fetal sheep (170.8 +/- 34.3 pg/ml; 120-140 days) than in intact fetal sheep (305.6 +/- 47.3 pg/ml). There were no differences, however, in the fetal plasma concentrations of total Met-Enk between the intact (18.0 +/- 1.9 ng/ml) and hypophysectomized (16.9 +/- 2.6 ng/ml) groups. During hypoxia, there were no changes in the fetal plasma concentrations of either free or total Met-Enk in the intact or hypophysectomized groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone (GH) stimulates insulin-like growth factor-I (IGF-I) and IGF-I-binding protein-3, but not GH receptor gene expression in livers of juvenile rats.

In the adult rat, expression of the liver GH receptor, insulin-like growth factor-I (IGF-I), and IGF-I-binding protein-3 (IGFBP-3) genes has been shown to be under GH control. Additionally, hypophysectomy and GH treatment have a differential effect on the relative abundance of liver IGF-I mRNA variants in adult rats. To further elucidate the time of appearance and the extent of GH control of liver GH receptor, IGF-I, and IGFBP-3 gene expression, we studied the effect of hypophysectomy and GH and IGF-I treatment in juvenile rats. Male Wistar rats were hypophysectomized (Hx) on postnatal day 26 and received twice daily sc injections of saline, recombinant human GH (2.5 U/kg.day), or recombinant human IGF-I (500 micrograms/kg.day) for 7 days. Sham-operated rats received the same treatment. Hx animals also received T4 (20 micrograms/kg.day). In Hx animals, there was a significant reduction in body weight (69.8 +/- 6.6 vs. 100.4 +/- 5.4 g; P < 0.001). GH, but not IGF-I, treatment increased body weight (79.6 +/- 9.6 g after GH vs. 69.8 +/- 6.6 g before GH; P < 0.05). GH treatment partially maintained liver, kidney, and lung weights in Hx animals and increased them in intact animals, whereas IGF-I treatment did so only in the lungs of intact and Hx animals. Serum GH and IGF-I levels were markedly reduced in Hx animals compared with those in intact controls, and GH treatment maintained, albeit partially, circulating IGF-I levels compared with those in saline-treated Hx animals. IGF-I mRNA levels were markedly reduced in Hx liver (25.0 +/- 5.4%; P < 0.001 compared with intact controls). GH treatment for 7 days increased IGF-I mRNA levels by 4.8-fold over the levels in 9-day Hx animals and increased IGF-I mRNA levels by 2.2-fold in control rats. Hypophysectomy decreased exon 2-containing transcripts by 7.0-fold and exon 1-containing transcripts by 4.1-fold. GH treatment, however, affected both exon 1- and exon 2-containing transcripts similarly. Hepatic IGFBP-3 mRNA levels were reduced in Hx (53.2 +/- 1.8%; P < 0.01 compared with intact controls) and IGF-treated Hx animals, but were not decreased in Hx GH-treated animals (100.6 +/- 9.5). No changes in GH receptor or GH-binding protein mRNA levels were caused by Hx, GH, or IGF-I treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of hypophysectomy and growth hormone on immune development in the domestic fowl

The effect of hypophysectomy and recombinant growth hormone (rcGH) treatment on the growth and development of the immune system was investigated in young chickens. Flow cytometric analysis of cell surface markers revealed no changes in the proportion of thymocytes expressing CT-1a, CD4, and/or CD8 among any of the treatment groups. In contrast, the proportion of both single positive CD4 and CD8 peripheral blood lymphocytes (PBL) was altered in hypox birds treated with rcGH compared to the vehicletreated group. Specifically, rcGH treatment produced a decrease in the proportion of CD8 + cells and an increase in the percentage of CD4 + PBL. There was little change in the labeling intensity of PBL or thymocytes associated with any treatment; however, double positive (CD4 +CD8 +) thymocytes from hypophysectomized chicks that were not given rcGH had increased fluorescence relative to rcGH supplemented hypox chicks. As expected, hypophysectomy reduced body, skeletal, and thymic growth. Treatment of hypox chicks with rcGH enhanced body weight while thymic weights were somewhat increased. Skeletal growth was not significantly altered by rcGH. Bursal growth appeared refractory to either treatment. These studies support the conclusion that growth hormone influences thymic growth and the maturation of thymus-derived lymphocytes. These results also demonstrate a biological activity for chicken growth hormone derived through recombinant technology.

Hypophysectomy of the cyclic mouse. I. Effects on folliculogenesis, oocyte growth, and follicle-stimulating hormone and human chorionic gonadotropin receptors.

The effects of hypophysectomy (HX) on folliculogenesis, oocyte growth, and ovarian FSH and LH receptors were examined by histology, topical autoradiography, and in vitro incubation of isolated follicles with [3H]thymidine. At random stages of the estrous cycle, mice were HX (Day 0), and they were killed from 0 to 20 days thereafter. Four days after HX, the number of preantral (stages 1-3) and antral (stages 4-5) follicles per ovary was reduced by 40% to 60% compared to Day 0 values, and stage 6 (large preovulatory) follicles had vanished. By Day 20 after HX, the numbers of follicles at stages 1, 2, and 4 were comparable to Day 4 values, whereas stage 3 and 5 follicles were still further diminished to 30% and 15% of Day 0 values, respectively. The number of atretic follicles from Days 0 to 20 after HX did not differ for follicles of stages 3-5, and stage 1 and 2 follicles were all healthy. However, oocyte growth was not coordinated with follicular growth after HX; the oocytes of stage 2-4 follicles were significantly larger than Day 0 oocytes. The enlarged oocytes appeared normal as judged by light and electron microscopy. DNA synthesis for stage 1-3 follicles declined significantly from Days 4 to 20 compared with Day 0 values, but did not change for stage 4 and 5 follicles, since atretic follicles at these stages were still labeled by [3H]thymidine and this was rare for Day 0 follicles. Topical autoradiography for [125I]-labeled FSH and hCG showed that follicular receptors for both hormones declined by Day 4 of HX and remained undetectable thereafter, except for trace amounts of [125I]-hCG binding in the interstitium. The decrease in follicular DNA synthesis and the greater diameter of oocytes in preantral follicles after HX suggest that longer transit times are required for one stage to progress to the next because of the anhormonal environment of the growing follicle. These results provide concrete evidence that pituitary gonadotropins are essential in the mouse for initiation, proliferation, and differentiation of all stages of growing follicles.

Effect of hypophysectomy on insulin-like growth factor (IGF)-1 binding activity of serum in chickens

1. 1. Hypophysectomy elevated IGF-1 binding activity of serum concurrently with decreases in circulating concentrations of IGF-1 and growth hormone (GH). 2. 2. When sera pooled from each experimental group were chromatographed on a Sephadex G-200 column, IGF-1 binding activity was mainly found in 150 and 30 kilodalton (kDa) proteins. 3. 3. Most of the serum IGF-1 were distributed among 150 kDa protein fractions. 4. 4. Hypophysectomy elevated IGF-1 binding activity of these proteins, especially that of 30 kDa protein. 5. 5. The binding of [ 125I]IGF-1 to the 30 kDa protein was inhibited by unlabelled IGF-1 but not by insulin, and saturated with a small amount of the ligand compared to the 150 kDa protein. 6. 6. The IGF-1 binding activity of 30 kDa protein was dependent on GH status of chickens.

Effects of hypophysectomy on galaninergic neurons in the rat hypothalamus.

To understand better the relationship between hypothalamic galaninergic neurons and the pituitary gland, we studied the effects of hypophysectomy on hypothalamic galanin (GAL) content and distribution by radioimmunoassay and immunohistochemistry, and on GAL mRNA by Northern blot analysis. Three weeks after hypophysectomy, performed at 5 or 8 weeks of age, the hypothalamic concentrations of GAL and GAL mRNA were reduced by 30-50% in both male and female rats, compared to age- and sex-matched controls. Similar reverse-phase HPLC retention times of hypothalamic GAL were observed in intact and hypophysectomized rats. The reduction of hypothalamic GAL concentration following hypophysectomy was time-dependent, as peptide levels were unaffected one week after surgery. Immunohistochemistry showed regional differences in the effect of hypophysectomy on galaninergic neurons. In the hypophysiotropic hypothalamus, the scarce GAL immunoreactivity normally observed in the arcuate nuclei was no longer detectable in hypophysectomized rats, and the intense GAL immunoreactivity of the external zone of the median eminence progressively decreased and completely disappeared 3 and 6 weeks after hypophysectomy. In contrast, in the neurohypophyseal system, there was an increase of GAL labelling of the perikarya and emerging axons in the supraoptic and lateral-paraventricular nuclei, 1 and 3 weeks after hypophysectomy, that disappeared 6 weeks after hypophysectomy. An increase of GAL immunoreactivity was also observed in the internal zone of the median eminence 1 week but not 3 weeks after hypophysectomy. We conclude that hypophysectomy reduces the content of GAL and GAL mRNA in the rat hypothalamus. These changes are time-dependent and clearly detected after 3 weeks. The neurohypophyseal and hypophysiotropic galaninergic systems respond differently to hypophysectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hypophysectomy and subsequent administrations of testosterone, triiodothyronine, and growth hormone on epidermal growth factor concentration in rat submandibular gland.

Effects of hypophysectomy and subsequent administrations of testosterone, triiodothyronine, and growth hormone on epidermal growth factor concentration in rat submandibular gland.

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)

Effect of hypophysectomy on rat preadipocyte replication and differentiation

Effect of hypophysectomy on rat preadipocyte replication and differentiation

Temporal gene expression is restored concomitantly with germ cells in the experimentally regressed rat testis.

The present study was designed to examine the effect of hypophysectomy and subsequent testosterone administration on germ cell numbers and germ cell- and Sertoli cell-specific mRNA levels in adult rats. Rats were hypophysectomized and 4 weeks later received 24-cm testosterone-containing polydimethylsiloxane (PDS) implants. Sham-hypophysectomized rats received an empty PDS implant. At 0 and 3 days, and at 1, 2, 4, and 8 weeks, rats were killed. One testis from each rat (n = 4/group) was used to prepare total RNA; the other testis was used to enumerate stage VII-VIII germ cells. cDNA probes for germ cell and Sertoli cell products were used to monitor germ cell- and Sertoli cell-specific mRNAs on Northern blots. Four weeks after hypophysectomy (0 days), preleptotene and pachytene spermatocytes and round and elongating spermatids were reduced in number to 54%, 12%, 1%, and 0%, respectively, of the control values. Testosterone administration caused a time-dependent increase in germ cell numbers; after 8 weeks of testosterone treatment, preleptotene and pachytene spermatocytes and round and elongating spermatids were 75%, 79%, 74%, and 22%, respectively, of control values. Lactate dehydrogenase-C, phosphoglycerate kinase-2, protamine-1, and sulfated glycoprotein-2 mRNA levels (on a per micrograms RNA basis) were 34%, 34%, less than 1%, and 580% of control values, respectively, 4 weeks after hypophysectomy and 79%, 87%, 61%, and 192% of control values, respectively, after 8 weeks of testosterone treatment. Pachytene spermatocyte and round spermatid numbers increased, while Sertoli cell sulfated glycoprotein-2 mRNA levels decreased, with respect to 4 week hypophysectomy values, as early as 3 days after implantation of testosterone capsules. In contrast, germ cell (lactate dehydrogenase-C, phosphoglycerate kinase-2, and protamine-1) mRNA levels increased to the greatest extent between 1-4 weeks after the start of testosterone treatment and, after a short lag period, reflected increases in germ cell type and number. The results indicate that cell-specific mRNAs appear concomitantly with germ cell reappearance in a time-dependent manner in the testes of testosterone-treated hypophysectomized adult rats.

Anatomical relationships in the patterns of insulin-like growth factor (IGF)-I, IGF binding protein-1, and IGF-I receptor gene expression in the rat kidney.

The rat kidney is both a target of circulating insulin-like growth factor-I (IGF-I) and a site of local IGF-I production. In order to identify which renal structures produce IGF-I and the functionally related IGF binding protein 1 (IGFBP-1), and which structures are potential sites of circulating or endogenous renal IGF action, we have employed in situ hybridization to localize IGF-I, IGFBP-1, and IGF-I receptor messenger RNAs (mRNAs) in the rat kidney. The effects of hypophysectomy (Hx) and GH replacement on renal IGF-I, IGFBP-1, and IGF-I receptor gene expression have also been evaluated. IGF-I and IGFBP-1 mRNAs are both localized in the epithelial cells of medullary thick ascending limbs (TALs) of Henle's loops in the normal rat kidney. IGF-I receptor mRNA is also abundant in TALs, but, in addition, is distributed throughout the distal nephron and collecting duct, and in the glomerulus, with lowest levels found in proximal tubules. Hx and GH treatment had complex effects on patterns of renal IGF-I and IGFBP-1 gene expression. In general, Hx resulted in decreased IGF-I and increased IGFBP-1 mRNA levels, and GH treatment produced the opposite effects, while IGF-I receptor mRNA levels were not significantly effected by either treatment. However, the most dramatic effect produced by the interruption of the pituitary-renal axis was the demonstration of reciprocal changes in IGF-I vs. IGFBP-1 gene expression in individual kidneys and even in individual nephrons, suggesting a local interaction between IGF-I and IGFBP-1 in the regulation of their respective mRNA levels. Functional implications issuing from these anatomical relationships in renal patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression are that IGF-I, if secreted into the tubular lumen, possibly carried or modulated by IGFBP-1, may act on luminal TAL and downstream receptor sites. The specific physiological role of IGF-I produced in TALs is open to speculation. Glomerular IGF-I receptor sites, based on their localization upstream and distant from local sources of IGF-I production, are predicted to be targets for circulating IGFs.

The effect of hypophysectomy on proluminal movement of 3H-androgens across the epididymal epithelium in the rat.

The effect of hypophysectomy on transepithelial movement of 3H-androgen in the rat epididymis was examined by using in vivo microperifusion of 3H-testosterone followed by in vivo micropuncture to obtain peritubular and intraluminal fluids. Experiments were performed on animals without hypophysectomy or on animals 5-6 days after hypophysectomy and 9-10 days after hypophysectomy. Tubules were perifused with Minimum Essential Medium containing 3H-testosterone. 14C-polyethyleneglycol was included in the perifusion fluid as a marker for contamination of the intraluminal fluid by peritubular fluid. Radioactivity of isotopes in the interstitial and intraluminal fluid was determined at 1 and 2 hours after perifusion and the percentage of peritubular isotopes appearing in the intraluminal fluid was determined. A sperm concentration microassay was performed on micropuncture samples from the epididymal tubules to assess testicular contribution to the lumen content. Proluminal movement of 3H-androgen and intratubular sperm concentrations in the caput epididymal tubules of rats 9-10 days after hypophysectomy were significantly decreased. Proluminal movement of 3H-androgen and intratubular sperm concentrations in the cauda epididymal tubules of rats 9-10 days after hypophysectomy were significantly increased. These results suggest that proluminal androgen movement is controlled by the presence of some testicular product in the epididymal lumen.

Effects of hypophysectomy on vascular insulin-like growth factor-I gene expression after balloon denudation in rats

Insulin-like growth factor-I (IGF-I) is a widely distributed mediator of the growth promoting effects of growth hormone (GH). We sought to determine whether the relationship between GH and IGF-I extends to the vascular system, where IGF-I is proposed to participate in the process of neointimal proliferation after balloon denudation. We show that in hypophysectomized rats basal aortic IGF-I mRNA is one-tenth that of normal rats and is increased after balloon denudation. The induction peaks at 7 days after balloon denudation at about 10-fold control levels, similar to normal rats. Treatment with GH restores basal IGF-I mRNA content to approximately half that of normal rats, without further increase in the relative magnitude of induction after balloon denudation. This local induction of IGF-I gene expression in the vessel wall following injury might explain why neointimal proliferation is not inhibited more profoundly after hypophysectomy.

Growth hormone (GH)-dependent hepatic GH receptors in the Japanese eel, Anguilla japonica: Effects of hypophysectomy and GH injection

Control mechanisms of growth hormone (GH) receptors in the eel liver were examined by following the time course of changes in total (MgCl 2-treated membranes) and free (untreated membranes) GH-binding sites after hypophysectomy and replacement therapy with homologous GH. Both total and free binding sites decreased significantly 1 week after hypophysectomy. Scatchard analysis indicated that the reduction in GH receptors was primarily due to a decrease in the number of binding sites, rather than to a change in binding affinity. When recombinant eel GH was injected intramuscularly into hypophysectomized eels (2 μg/g body wt), plasma GH concentration increased to a maximal value after 10 hr and decreased to the initial level by 72 hr. Free binding sites decreased to a minimal value 24 hr after the injection and returned to the initial level after 72 hr. The reduction in free binding sites seems to be due to occupation of GH receptors. Total binding sites increased gradually to almost twofold over those of the controls 5 days after the injection, the increase being due to an increase in the binding capacity. GH appears to be importantly involved in inducing and maintaining its own receptors in the eel liver.