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Doctor of Diet and Nutrition Sciences ME-823 Semester - 3

Week # 3: Lecture # 1 & 2

Vitamin D
Vitamin D is a lipid hormone derived from cholesterol. In contrast to other vitamins, its active
form is not available in the diet. Instead, vitamin D requires activation through a series of metabolic
steps. This means that activated vitamin D deficiency can develop in people on a normal diet, for
example in cases of renal failure. Vitamin D exists in several forms:
• Vitamin D2 (ergocalciferol) is absorbed from the gut from plants and fungi; it is also used
in some vitamin supplements
• Vitamin D3 (cholecalciferol) is synthesised from 7-dehydrocholesterol in the skin on
exposure to sunlight; vitamin D3 can also be absorbed from the gut from foods such as oily
fish, milk and eggs, but because it is very difficult to obtain enough vitamin D3 from the
diet, synthesis on exposure to sunlight is the main source (Table 1.5)
• 25-Hydroxyvitamin D (calcifediol) is synthesized in the liver from hydroxylation of
vitamin D3 and vitamin D2
• 1,25-Dihydroxyvitamin D (calcitriol) is the biologically active form of vitamin D; it is
produced when 25-hydroxyvitamin D is hydroxylated in the kidneys

Actions
In calcium and phosphate homeostasis, active vitamin D
facilitates calcium and phosphate absorption from the gut.
Vitamin D deficiency can result in demineralisation of
bones, causing rickets in children and osteomalacia in
adults. Risk factors include malnutrition, inadequate
exposure to sunlight, dark skin pigmentation and obesity.
In the bone, active vitamin D stimulates activation of
osteoclasts to enhance bone resorption. In the kidneys, it
increases the effect of PTH in the renal tubular
reabsorption of calcium.
Vitamin D receptors are expressed in many cell types throughout the body, including immune
cells, neurones and skin cells.
Doctor of Diet and Nutrition Sciences ME-823 Semester - 3

Synthesis
Steps in the synthesis of active 1,25-
dihydroxyvitamin D are shown in Figure

• Vitamin D3 (cholecalciferol) is either


synthesized in the skin or absorbed from the gut,
along with vitamin D2 (ergocalciferol).
• Vitamin D2 and D3 undergo hydroxylation in the
liver to produce 25-hydroxyvitamin D.
• The final hydroxylation and activation occurs in
the kidney (catalysed by PTH) resulting in the
formation of 1,25-hydroxyvitamin D.

Receptors
The vitamin D receptor is a nuclear receptor. It is activated by the binding of 1,25-
dihydroxyvitamin D. The activated receptor then forms a transcription factor that facilitates gene
transcription. The role of the vitamin D receptor is best understood in the following:
• In the bone, binding of 1,25-dihydroxyvitamin D to the receptor causes activation of
osteoclasts (specialised cells involved in reabsorption of bone)
• In the gut, activation of the vitamin D receptor facilitates absorption of calcium and
phosphate

The hypothalamus

The hypothalamus is an almond-sized symmetrical structure in the brain. It is below and anterior
to the thalamus, superior to the pituitary gland and either side of the 3rd ventricle. As an
endocrine gland, the hypothalamus is responsible for control of the pituitary gland. It also has
major effects on other, non-endocrine physiological processes, such as regulation of body
temperature.

Embryology
The hypothalamus develops from the neural tube at about 5 weeks’ gestation. The neural tube is
a group of cells that develops into the brain, spinal cord and autonomic ganglia. The neural origin
Doctor of Diet and Nutrition Sciences ME-823 Semester - 3

of the hypothalamus underlies its role as a neuroendocrine gland and allows neural connections
with many other parts of the central nervous system, such as the thalamus and the midbrain, which
determine the hypothalamus’s wide-ranging effects on the body.

Anatomy
The hypothalamus is surrounded by the thalamus
laterally and superiorly. The medial border is the
wall of the 3rd ventricle, and the inferior border
includes the pituitary stalk, a structure
connecting the hypothalamus and posterior
pituitary and the continuation of the floor of the
3rd ventricle.

There are three main anatomical areas of the hypothalamus (medial, paraventricular and lateral),
some of which share neuroendocrine functions:

• The medial hypothalamus has projections to the paraventricular hypothalamus as well as


the anterior and posterior pituitary glands; it regulates higher functions such as body
temperature, appetite, thirst, the sleep−wake cycle and sexual behavior.
• The paraventricular hypothalamus, which borders the 3rd ventricle, has neurones that
project to the anterior and posterior pituitary glands.
• The lateral hypothalamus is a ‘relay centre’ containing the medial forebrain bundles,
which have neuronal connections

Histology
The hypothalamus consists of neurones (nerve cells) and neuroendocrine cells (cells that receive
neuronal input and release hormones into the blood). The neuroendocrine cells synthesize two sets
of hormone:
• The first set are hormones (i.e. antidiuretic hormone and oxytocin) are synthesized in the
hypothalamus and transported down axons for storage and release from the posterior
pituitary gland
• The second set are hormones (e.g. growth hormone−releasing hormone, GHRH;
somatostatin; corticotrophin-releasing hormone, CRH; thyrotropin releasing hormone,
TRH; gonadotrophin-releasing hormone, GnRH; and dopamine) are synthesized in the
Doctor of Diet and Nutrition Sciences ME-823 Semester - 3

hypothalamus and reach the anterior pituitary gland through the hypothalamic−pituitary
portal system (a network of arteries and capillaries carrying blood from the hypothalamus
to the anterior pituitary) to stimulate or inhibit secretion of anterior pituitary hormones.

Physiology
The hypothalamus is considered the body’s ‘master control center’ for hormone secretion. In this
role, it controls and receives signals from other endocrine glands. End organs controlled by the
hypothalamus through hormones released by the anterior pituitary include:
• thyroid gland
• adrenal glands
• gonads
Body temperature is controlled by the hypothalamus, which also has effects on appetite and thirst,
the sleep−wake cycle and sexual behavior.

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