Suppression of puberty in rats by exercise: effects on hormone levels and reversal with GnRH infusion

1991 ◽  
Vol 260 (4) ◽  
pp. R717-R723 ◽  
Author(s):  
J. M. Manning ◽  
F. H. Bronson

In an effort to better understand the effects of prolonged exercise on the hypothalamic-pituitary-ovarian axis, we made a variety of comparisons between young female rats in two treatment groups: 1) prolonged exercise, in which growth and reproductive development were arrested at a peripubertal stage by requiring rats to run for long periods of time in order to obtain food; and 2) voluntary exercise, in which same-aged control rats were fed ad libitum and given free access to a running wheel. The pulsatile secretion of luteinizing hormone (LH) and growth hormone were completely suppressed by the prolonged exercise treatment. Mean levels of follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone were not affected. Prolonged exercise elevated corticosterone titers, and the secretory pattern of this steroid was changed out of phase with running activity. Tissue levels of gonadotropin-releasing hormone (GnRH) in the hypothalamus and LH in the pituitary were enhanced, not suppressed, by prolonged exercise. Most importantly, pulsatile infusions of GnRH reinstated normal pubertal development and ovulation in rats still growth restricted by the prolonged exercise treatment. The results of this study indicate that the suppressive effects of prolonged exercise somehow affect the production of the hypothalamic GnRH-pulse generator signal.

1989 ◽  
Vol 257 (6) ◽  
pp. R1359-R1364 ◽  
Author(s):  
J. M. Manning ◽  
F. H. Bronson

Immature female rats were required to run for prolonged periods of time to obtain food. The amount of food they earned was adequate for full pubertal development and moderate growth under nonworking conditions, but both processes were blocked by the exercise requirement. Prolonged exercise also blocked the pulsatile release of luteinizing hormone (LH); only two LH pulses were seen in seven exercising females during a total of 24 h of monitoring at 8 wk of age. By comparison, almost 1 pulse/h was seen in postpubertal, normally growing females of this same age during metestrus. When the exercising females' running requirement was relaxed at 8 wk of age they experienced rapid catch-up growth and reproductive development. Both basal secretion and LH pulse frequency increased markedly within 48 h, and most of these females ovulated during the third dark period after relaxation. Altogether, the experimental paradigm and techniques employed here yield highly predictable results, and they should prove useful for exploring other neuroendocrine pathways through which excessive exercise antagonizes reproduction.


2016 ◽  
Vol 231 (3) ◽  
pp. 197-207 ◽  
Author(s):  
Iulia Potorac ◽  
Adolfo Rivero-Müller ◽  
Ashutosh Trehan ◽  
Michał Kiełbus ◽  
Krzysztof Jozwiak ◽  
...  

Glycoprotein hormones are complex hormonally active macromolecules. Luteinizing hormone (LH) is essential for the postnatal development and maturation of the male gonad. Inactivating Luteinizing hormone beta (LHB) gene mutations are exceptionally rare and lead to hypogonadism that is particularly severe in males. We describe a family with selective LH deficiency and hypogonadism in two brothers. DNA sequencing of LHB was performed and the effects of genetic variants on hormone function and secretion were characterized by mutagenesis studies, confocal microscopy and functional assays. A 20-year-old male from a consanguineous family had pubertal delay, hypogonadism and undetectable LH. A homozygous c.118_120del (p.Lys40del) mutation was identified in the patient and his brother, who subsequently had the same phenotype. Treatment with hCG led to pubertal development, increased circulating testosterone and spermatogenesis. Experiments in HeLa cells revealed that the mutant LH is retained intracellularly and showed diffuse cytoplasmic distribution. The mutated LHB heterodimerizes with the common alpha-subunit and can activate its receptor. Deletion of flanking glutamic acid residues at positions 39 and 41 impair LH to a similar extent as deletion of Lys40. This region is functionally important across all heterodimeric glycoprotein hormones, because deletion of the corresponding residues in hCG, follicle-stimulating hormone and thyroid-stimulating hormone beta-subunits also led to intracellular hormone retention. This novel LHB mutation results in hypogonadism due to intracellular sequestration of the hormone and reveals a discrete region in the protein that is crucial for normal secretion of all human glycoprotein hormones.


1977 ◽  
Vol 73 (2) ◽  
pp. 289-300 ◽  
Author(s):  
R. GHRAF ◽  
E. R. LAX ◽  
W. WAGNER ◽  
H. SCHRIEFERS

SUMMARY The NADP-dependent microsomal kidney enzymes, 3α- and 20β-hydroxysteroid dehydrogenase (HSDH), which exhibit considerable sex differences in their activities (male: female activity ratios, 16:1 and 30:1 respectively), were investigated after interference with the pituitary–gonad and pituitary–adrenal systems. Prepubertal gonadectomy as well as hypophysectomy of mature male rats led to a decline in HSDH activity to almost that found in the normal female rat, whereas activities in female rats were unaffected. Testosterone induced typical male 3α-HSDH activity in both gonadectomized and hypophysectomized rats of either sex. Administration of 5α-dihydrotestosterone (5α-DHT) or 5α-androstane-3α, 17β-diol to hypophysectomized male rats was equally effective in restoring full 3α- and 20β-HSDH activities whereas 5α-androstane-3β, 17β-diol was less effective and dehydroepiandrosterone was ineffective. Simultaneous administration of cyproterone acetate did not block the inductive action of 5α-DHT. Administration of chorionic gonadotrophin, pregnant mare serum gonadotrophin or a combination of luteinizing hormone and follicle-stimulating hormone to hypophysectomized male rats all led to parallel increases in the weight of the seminal vesicles and in both renal enzyme activities; administration of growth hormone, prolactin or thyroid-stimulating hormone was ineffective. Adrenalectomy of gonadectomized, but not of hypophysectomized male rats, caused a further drop in activity to the normal female level. Adrenalectomy of otherwise intact rats did not affect either enzyme activity. The hypophysis was involved in the regulation of the two NADP-dependent renal HSDH activities through its gonadotrophic function in male rats; adrenal secretions were of little physiological significance.


1983 ◽  
Vol 96 (4) ◽  
pp. 1172-1177 ◽  
Author(s):  
M Chambard ◽  
B Verrier ◽  
J Gabrion ◽  
J Mauchamp

When cultured in collagen gel-coated dishes, thyroid cells organized into polarized monolayers. The basal poles of the cells were in contact with the collagen gel, whereas the apical surfaces were facing the culture medium. Under these culture conditions, thyroid cells do not concentrate iodide nor respond to acute stimulation by thyroid-stimulating hormone (TSH). To allow the free access of medium components to the basal poles, the gel was detached from the plastic dish and allowed to float in the culture medium. After release of the gel, the iodide concentration and acute response to TSH stimulation were restored. Increased cAMP levels, iodide efflux, and formation of apical pseudopods were observed. When the thyroid cells are cultured on collagen-coated Millipore filters glued to glass rings, the cell layer separates the medium in contact with the apical domain of the plasma membrane (inside the ring) from that bathing the basolateral domain (outside the ring). Iodide present in the basal medium was concentrated in the cells, whereas no transport was observed when iodide was added to the luminal side. Similarly, an acute effect of TSH was observed only when the hormone was added to the basal medium. These results show that the iodide concentration mechanism and the TSH receptor-adenylate cyclase complex are present only on the basolateral domain of thyroid cell plasma membranes.


1990 ◽  
Vol 259 (1) ◽  
pp. R25-R31 ◽  
Author(s):  
F. H. Bronson ◽  
P. D. Heideman

These studies focused on the phenomenon of "catch-up" pubertal development. Circulating levels of several hormones were characterized in 8-wk-old female rats whose growth and reproductive development had been blocked before puberty by restricting their food intake. Some of these females were fed ad libitum for 24 h to initiate rapid pubertal development. Blood levels of luteinizing hormone (LH) and growth hormone (GH) were suppressed by food restriction and then partially restored to adult diestrus levels by 24 h of ad libitum feeding. Prolactin titers were also suppressed by food restriction but not significantly elevated by 24 h of ad libitum feeding. Circulating levels of follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were unaffected by either treatment. It is concluded that GH could play an active supplementary role to LH in eliciting catch-up pubertal development but that FSH and TSH could play only passive roles at best. The role of prolactin remains uncertain. On a finer time scale, when food-restricted females were examined in relation to the time of day at which they were fed, most showed high-amplitude LH pulses 2-4 h after eating but rarely at any other time. Thus under some conditions LH secretion can be modulated by food intake on an almost hour-by-hour basis. Overall, blood levels of corticosterone were generally but not always inversely correlated with the frequency of LH pulsing in these experiments. Finally, the present results argue against the concept that puberty is dependent on a critical whole body characteristic.(ABSTRACT TRUNCATED AT 250 WORDS)


1961 ◽  
Vol 38 (4) ◽  
pp. 577-584 ◽  
Author(s):  
Sven Erik Björkman ◽  
Torsten Denneberg ◽  
Inge Hedenskog

ABSTRACT A method for demonstrating the presence of a thyroid stimulating factor in the blood of patients with progressive exophthalmos after thyroidectomy or after treatment with radioiodine is described. The method consists of transfusing freshly drawn blood from the patients to euthyroid recipients and subsequently following the PBI level of the recipients at regular intervals. Six exophthalmic patients tested in this manner were found to have such a factor in their circulating blood. After transfusion of their blood a significant rise in the PBI level of the recipients could be demonstrated. Two other patients, one with exophthalmos of long duration did not show this response nor did it occur after transfusion of blood from two control subjects. In one case the action of this factor was compared with that of animal thyrotrophin and found to be of the same magnitude.


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