Effects of Pituitary Hormone Deficiency on Growth and Glucose Metabolism of the Sheep Fetus

Pituitary hormones are essential for normal growth and metabolic responsiveness after birth, but their role before birth remains unclear. This study examined the effects of hypophysectomizing fetal sheep on their growth and glucose metabolism during the late normal and extended periods of gestation, and on their metabolic response to maternal fasting for 48 h near term. Fetal hypophysectomy reduced crown rump length (CRL), limb lengths, and body weight but increased ponderal index relative to controls near normal term. It also lowered the daily rate of crown rump length increment uniformly from 35 d before, to 20 d after normal term. Hypophysectomized (HX) fetuses had normal weight-specific rates of umbilical uptake, utilization, and oxidation of glucose but lower rates of umbilical oxygen uptake than controls near term. All these metabolic rates were significantly less in HX fetuses during the extended period of gestation than in HX and intact fetuses near normal term. In contrast to controls, glucogenesis was negligible in HX fetuses during maternal fasting. Consequently, the rate of glucose utilization decreased significantly in fasted HX but not intact fetuses. Conversely, the rate of CO2 production from glucose carbon decreased in fasted intact but not HX fetuses. Fetal hypophysectomy also prevented the fasting-induced increases in plasma cortisol and norepinephrine concentrations seen in controls. These findings demonstrate that the pituitary hormones are important in regulating the growth rate and adaptive responses of glucose metabolism to undernutrition in fetal sheep. They also suggest that fetal metabolism is altered when gestational length is extended.

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Identification of a Novel PROP1 Mutation in a Patient with Combined Pituitary Hormone Deficiency and Enlarged Pituitary

International Journal of Molecular Sciences ◽

10.3390/ijms20081875 ◽

2019 ◽

Vol 20 (8) ◽

pp. 1875 ◽

Cited By ~ 3

Author(s):

Laura Penta ◽

Carla Bizzarri ◽

Michela Panichi ◽

Antonio Novelli ◽

Francesca Romana Lepri ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Novel Mutation ◽

Pituitary Hormones ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Pituitary Hormone Deficiency ◽

Combined Pituitary Hormone Deficiency ◽

Familial Cases ◽

Number Of Patients

Growth hormone deficiency (GHD) can be present from the neonatal period to adulthood and can be the result of congenital or acquired insults. In addition, GHD can be classified into two types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). CPHD is a disorder characterized by impaired production of two or more anterior and/or posterior pituitary hormones. Many genes implicated in CPHD remain to be identified. Better genetic characterization will provide more information about the disorder and result in important genetic counselling because a number of patients with hypopituitarism represent familial cases. To date, PROP1 mutations represent the most common known genetic cause of CPHD both in sporadic and familial cases. We report a novel mutation in the PROP1 gene in an infant with CPHD and an enlarged pituitary gland. Close long-term follow-up will reveal other possible hormonal defects and pituitary involution.

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The pituitary and hypopituitarism

Paediatric Endocrinology and Diabetes ◽

10.1093/med/9780198786337.003.0003 ◽

2020 ◽

pp. 83-120

Author(s):

Gary Butler ◽

Jeremy Kirk

Keyword(s):

Anterior Pituitary ◽

Pituitary Hormones ◽

Thyroid Stimulating Hormone ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Sexual Characteristics ◽

Biochemical Assessment ◽

Cranial Diabetes Insipidus ◽

Clinical Problems ◽

Stimulating Hormone

• The pituitary is formed of two anatomically and embryologically distinct lobes: ◦ anterior pituitary: which secretes growth hormone (GH), gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and prolactin ◦ posterior pituitary: which secretes vasopressin and oxytocin. • Hypopituitarism is deficiency of one or more pituitary hormones. Some hormones, e.g. GH (LH/FSH), are more likely to present with isolated deficiencies, while others, e.g. TSH, ACTH, are more often found as part of multiple pituitary hormone deficiency (MPHD). • Deficiencies may be congenital (including genetic) or acquired; secondary to tumour, trauma, infiltration, infection, or irradiation. • GH deficiency: ◦ diagnosed using a combination of clinical, radiological, and biochemical assessment (including GH stimulation testing) ◦ treatment is with GH (including if necessary into adulthood). • LH/FSH deficiency: ◦ If acquired, often one of the first anterior pituitary hormones to be lost. ◦ Congenital forms: ■ present with cryptorchidism and/or micropenis in males ■ may occur in isolation, or in association with anosmia (Kallmann and CHARGE syndromes). ◦ Treatment: sex steroid therapy to induce secondary sexual characteristics, and recombinant FSH/LH to induce fertility potential. • ACTH deficiency: ◦ Unlike primary adrenal problems, hyperpigmentation does not occur. ◦ Although mineralocorticoid production is preserved, hyponatraemia may still occur. ◦ Treatment is with hydrocortisone. • TSH deficiency: ◦ TSH may be low, normal, or raised (but inappropriate for free thyroxine level). ◦ Treatment is with thyroxine. • Vasopressin deficiency: ◦ produces cranial diabetes insipidus ◦ treatment is with DDAVP (orally or nasally). • Prolactin and oxytocin deficiency rarely produce clinical problems.

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Growth Hormone Deficiency in Children and Adult Patients with Hypopituitarism: Challenges in the Diagnosis and Management

Endocrinology and Disorders ◽

10.31579/2640-1045/004 ◽

2017 ◽

Vol 1 (1) ◽

pp. 01-04

Author(s):

Mansour Hosseinlou

Keyword(s):

Growth Hormone ◽

Pituitary Gland ◽

Growth Hormone Deficiency ◽

Medical Condition ◽

Pituitary Hormones ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Diagnosis And Management ◽

Treatment Regimens

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain.If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism is used. Hypopituitarism is a complex medical condition associated with increased morbidity and mortality, requires complicated treatment regimens, and necessitates lifelong follow up by the endocrinologist.

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Effects of pancreatectomy on the growth and metabolite concentrations of the sheep fetus

Journal of Endocrinology ◽

10.1677/joe.0.1100225 ◽

1986 ◽

Vol 110 (2) ◽

pp. 225-231 ◽

Cited By ~ 19

Author(s):

A. L. Fowden ◽

X. Z. Mao ◽

R. S. Comline

Keyword(s):

Body Weight ◽

Plasma Insulin ◽

Plasma Concentrations ◽

Amino Nitrogen ◽

In Utero ◽

The Body ◽

Fetal Sheep ◽

Crown Rump Length ◽

Metabolite Concentrations ◽

Near Term

ABSTRACT The effects of fetal pancreatectomy on the growth and metabolism of the fetal sheep were investigated in chronically catheterized animals during the last third of gestation. Fetal pancreatectomy reduced body weight and crown–rump length at delivery near term (term 145 days). Body weight was affected more than body length so the ratio of weight to length was significantly less after pancreatectomy than in intact animals (P < 0·05). Pancreatectomized fetuses appeared to maintain a normal growth rate for 5–10 days after surgery but thereafter showed no further significant increase in body weight. When all the data from the intact and pancreatectomized fetuses were combined, there was a significant positive correlation between the plasma insulin concentration in utero and the body weight at delivery near term. The majority of organs studied were reduced in absolute weight after pancreatectomy but only the spleen and thymus were proportionally lighter when the weights were expressed as a percentage of body weight. Brain and placental weights were similar in intact and pancreatectomized fetuses. Over the range of values observed in utero, there were significant inverse correlations between the log plasma insulin level and the mean plasma concentrations of glucose, lactate, fructose and α-amino-nitrogen in individual intact and pancreatectomized fetuses. Insulin infusion into pancreatectomized fetuses restored the metabolite concentrations to their normal values within 48 h of infusion. The results demonstrate that insulin has a vital role in regulating fetal growth and metabolism in utero. J. Endocr. (1986) 110, 225–231

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Guidelines for patients with the hypothalamo-pituitary disorders; School for patients

Problems of Endocrinology ◽

10.14341/probl12088 ◽

1996 ◽

Vol 42 (5) ◽

pp. 32-33

Author(s):

G. A. Melnichenko ◽

T. I. Romantsova ◽

V. A. Chernogolov ◽

M. G. Pavlova

Keyword(s):

Pituitary Gland ◽

Head Injuries ◽

Pituitary Hormones ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Common Symptom ◽

General Weakness ◽

Direct Pressure ◽

Principles Of Treatment ◽

Healthy Part

In the previous issue, we talked about the structure and functions of the hypothalamic-pituitary system, as well as the need to create schools to help patients with hypothalamic-pituitary disorders. Today we want to focus on the manifestations of pituitary hormone deficiency and the basic principles of treatment of this pathology. Lack of pituitary hormones If the pituitary gland does not produce certain hormones or produces them in small quantities, then this condition is called hypopituitarism. Most often, this condition occurs due to the presence of a benign (i.e., non-cancerous) tumor of the pituitary gland or hypothalamus. If a person has a pituitary tumor, it can lead to a decrease in its functions by direct pressure of the tumor mass on the healthy part of the pituitary gland or as a result of surgical treatment or irradiation of the tumor. Less commonly, hypopituitarism is caused by infectious diseases of the brain (such as meningitis), significant blood loss (for example, during childbirth), head injuries, as well as rare diseases (sarcoidosis, etc.). I. Lack of ACTH. 1. What are the symptoms of ACTH deficiency? The most common symptom is fatigue, a feeling of general weakness, sometimes dizziness. Some patients have nausea and diarrhea.

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GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies

Acta Endocrinologica ◽

10.1530/eje-09-0319 ◽

2009 ◽

Vol 161 (suppl_1) ◽

pp. S85-S95 ◽

Cited By ~ 29

Author(s):

Helena Filipsson ◽

Gudmundur Johannsson

Keyword(s):

Replacement Therapy ◽

Pituitary Hormones ◽

Hormone Deficiency ◽

Dose Titration ◽

Pituitary Hormone ◽

Adult Women ◽

Central Hypothyroidism ◽

Gh Replacement ◽

Oral Estrogen ◽

Hormonal Interactions

Severe GH deficiency (GHD) in adults has been described as a clinical entity. However, some of the features associated with GHD could be due to unphysiological and inadequate replacement of other pituitary hormone deficiencies. This may be true for glucocorticoid replacement that lacks a biomarker making dose titration and monitoring difficult. Moreover, oral estrogen replacement therapy decreases IGF1 levels compared with the transdermal route, which attenuates the responsiveness to GH replacement therapy in women. In addition, in untreated female hypogonadism, oral estrogen may augment the features associated with GHD in adult women. Important interactions between the hormones used for replacing pituitary hormone deficiency occur. Introducing GH replacement may unmask both an incipient adrenal insufficiency and central hypothyroidism. Therefore, awareness and proper monitoring of these hormonal interactions are important in order to reach an optimal replacement therapy. This review will focus on the complex hormonal interactions between GH and other pituitary hormones in GHD and in GH replacement.

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Contribution of fructose and lactate produced in placenta to calculation of fetal glucose oxidation rate

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.5.e834 ◽

1995 ◽

Vol 269 (5) ◽

pp. E834-E839 ◽

Cited By ~ 2

Author(s):

J. E. McGowan ◽

P. W. Aldoretta ◽

W. W. Hay

Keyword(s):

Glucose Metabolism ◽

Oxidative Metabolism ◽

Oxidation Rate ◽

Glucose Oxidation ◽

Co2 Production ◽

Direct Oxidation ◽

Fetal Sheep ◽

Metabolic Substrate ◽

Metabolic Products

We examined the rate of production of [14C]fructose and [14C]lactate from [U-14C]glucose by the placenta and the contribution of 14CO2 from fetal oxidation of these metabolic products to the calculation of glucose oxidation rate in fetal sheep. During fetal tracer infusions (n = 16), oxidation of fructose contributed 16 +/- 3% of total fetal CO2 production; oxidation of lactate accounted for 3.3 +/- 0.1%. Thus 80% of total fetal CO2 production resulted from direct oxidation of carbon atoms in glucose; the "direct" glucose oxidation fraction was 0.46 +/- 0.04. During maternal tracer infusion (n = 15), CO2 production from fructose was 21 +/- 3, 20 +/- 3, and 30 +/- 4% and from lactate was 16 +/- 3, 13 +/- 3, and 11 +/- 4% in hypo-, normo-, and hyperglycemic animals, respectively; the direct glucose oxidation fraction was 0.40 +/- 0.04, not different from the fraction obtained with the fetal tracer infusion. Fetal oxidation of substrates derived from glucose metabolism in the placenta contributes significantly to fetal CO2 production. Fetal oxidation of placental products of a metabolic substrate tracer should be considered in studies of fetal oxidative metabolism.

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