1. Hypothalamus & Pituitary Gland

2. The Pituitary Gland and Hypothalamus
The pituitary gland (hypophysis) is located at the base of the brain, immediately below the hypothalamus. It is connected to the hypothalamus by a pituitary stalk
The pituitary gland (hypophysis) is located at the base of the brain, immediately below the hypothalamus. It is connected to the hypothalamus by a pituitary stalk.
It comprises 2 lobes: anterior (adenohypophysis) and posterior (neurohypophysis).
The posterior pituitary is an extension of the hypothalamus, and consists of neural tissue. The cell bodies of certain neurons which are located in the hypothalamus send their axons down the stalk to the posterior pituitary, where they end close to capillaries.
The anterior pituitary in contrast has no direct neural connection to the brain. Its functional connection to the hypothalamus is through blood: blood from the hypothalamus drains into capillaries of the anterior pituitary. This allows “controlling hormones” to travel directly from the hypothalamus to the anterior pituitary.

3. Pituitary-Hypothalamic relationships
The pituitary gland comprises 2 lobes: posterior (neurohypophysis) and anterior (adenohypophysis)
The posterior pituitary is an extension of the hypothalamus, and consists of neural tissue
The hormones are synthesised in the hypothalamus neurons.
They are transported down the axons and stored in vesicles in the axon ending located in the posterior pituitary
Nerve impulses travel down axons into the posterior pituitary.
This causes the release of the vesicles of hormones into the blood stream at the posterior pituitary

4. Pituitary-Hypothalamic relationships
The anterior pituitary has no direct neural connection to the brain.
⟶ Blood from the hypothalamus drains into capillaries of the anterior pituitary
⟶ releasing and release-inhibiting hormones are carried in the blood to the anterior pituitary to regulate hormone release

5. Hormone
Secretion

6. Morphology
The pituitary gland (hypophysis) is located in a small depression in the sphenoid bone, the sella turcica, just beneath the hypothalamus
It is connected to the hypothalamus by a thin stalk called the infundibulum
Sella turcica

7. Histology of the Anterior Lobe
Most of the cells in the anterior lobe (adenohypophysis) contain secretory granules, although some are only sparsely granulated
Based on their characteristic staining with standard histochemical dyes and immunofluorescent stains, it is possible to identify the cells that secrete each of the pituitary hormones

8. Histology of the Posterior Lobe
The posterior lobe (neurohypophysis) consists of two major portions:
the infundibulum, or stalk,
and the infundibular process, or neural lobe
The posterior lobe is richly endowed with fibers
The cell bodies from which these fibers arise are located in the hypothalamus
Secretory material synthesized in cell bodies in the hypothalamus is transported down the axons and stored in in the posterior lobe

9. Physiology of the Posterior Pituitary
The posterior pituitary gland secretes two hormones which are:
oxytocin ,
increase uterine contractions during parturition
Contraction of mammary glands to secret milk
and vasopressin or arginine vasopressin (AVP) (or Antidiuretic Hormone ‘ADH’)
contract vascular smooth muscle and thus raise blood pressure
promote reabsorption of water by renal tubules

10. Physiology of the Posterior Pituitary
Oxytocin and AVP are stored in and secreted by the posterior pituitary gland, but are synthesized by the hypothalamus

11. Regulation of Posterior Pituitary Function
Regulation of oxytocin secretion showing a positive feedback arrangement.
Increased blood osmolality or decreased blood volume are sensed in the brain or thorax, respectively, and increase vasopressin secretion.

12. Posterior Pituitary hormones
The posterior pituitary secretes two peptide hormones:
⟶ oxytocin (OT)
⟶ antidiuretic hormone (ADH); also known as vasopressin

13. Oxytocin
Stimulates uterine contractions during childbirth by mobilizing Ca2+ through a second-messenger system
Also triggers milk ejection (“letdown” reflex) in women producing milk
Plays a role in sexual function in males and females
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14. Antidiuretic Hormone (ADH)
Osmoreceptors in the hypothalamus respond to changes in the solute concentration of the blood plasma
If solute concentration is high
⟶ Osmoreceptors depolarize and transmit impulses to hypothalamic neurons
⟶ ADH is synthesized and released, inhibiting urine formation by the kidneys

15. Physiology of the Anterior Pituitary Gland
There are six anterior pituitary hormones whose physiological importance is clearly established
They include the hormones that govern the function of the:
thyroid and adrenal glands,
the gonads,
the mammary glands,
and bodily growth

16. Hormones of the Anterior Pituitary Gland
All the anterior pituitary hormones are proteins or glycoproteins
They are divided into 3 categories according to structure similarity:
Glycoprotein Hormones
Growth hormone and prolactin
Adrenocorticotropin family

17. Glycoprotein Hormones
Target
Major actions in humans
Thyroid-stimulating hormone (TSH), also called thyrotropin
Thyroid gland
Stimulates synthesis and secretion of thyroid hormones
Follicle-stimulating hormone (FSH)
Ovary
Stimulates growth of follicles and estrogen secretion
Testis
Acts on Sertoli cells to promote maturation of sperm
Luteinizing hormone (LH)
Stimulates ovulation of ripe follicle
and formation of corpus luteum;
stimulates estrogen and progesterone synthesis by corpus luteum
Stimulates interstitial cells of Leydig to synthesize and secrete testosterone

18. Growth Hormone and Prolactin
Somatotropes (GH producing cells) are by far the most abundant anterior pituitary cells, and account for at least half the cells
Structurally, prolactin (PRL) is closely related to GH
Hormone
Target
Major actions in humans
Growth hormone (GH), also called somatotropic hormone (STH)
Most tissues
Promotes growth in stature and mass;
stimulates production of insulin-like growth factor (IGF-I);
stimulates protein synthesis;
usually inhibits glucose utilization and promotes fat utilization
Prolactin
Mammary glands
Promotes milk secretion and mammary growth

19. Adrenocorticotropin Family
The ACTH related peptides constitute a family because:
they contain regions of homologous amino acid sequences, which may have arisen through exon duplication,
and because they all are encoded in the same gene
Hormone
Target
Major actions in humans
Adrenocorticotropic hormone (ACTH), also known as adreno-corticotropin or corticotropin
Adrenal cortex
Promotes synthesis and secretion of adrenal cortical hormones
β-Lipotropin
Adipose
Tissue
Physiological role not established

20. Regulation of Anterior Pituitary Function
Secretion of the anterior pituitary hormones is regulated by:
the central nervous system
provides the primary drive for secretion
and hormones produced in peripheral target glands
and peripheral input plays a secondary, though vital, role in modulating secretory rates
Secretion of all the anterior pituitary hormones except PRL declines severely in the absence of stimulation from the hypothalamus as can be produced
when the pituitary gland is removed surgically from its natural location and reimplanted at a site remote from the hypothalamus
PRL secretion is normally under tonic inhibitory control by the hypothalamus

21. Feedback Control of Anterior Pituitary Function
Environmental factors may increase or decrease pituitary activity by increasing or decreasing hormone secretions from hypothalamus
Pituitary secretions increase the secretion of target gland hormones, which may inhibit further secretion by acting at either the hypothalamus or the pituitary
Pituitary hormones may also inhibit their own secretion by a short feedback loop

22. Anterior Pituitary hormones
All are proteins
All except GH activate cyclic AMP second-messenger systems at their targets
TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of other endocrine glands)

23. Growth Hormone (GH)
Stimulates cell division - targets bone and skeletal muscle
Promotes protein synthesis and encourages use of fats for fuel
Most effects are mediated indirectly by insulin-like growth factors (IGFs)
Like several other hormones, growth hormone is secreted in a rhythmic fashion, with secretion occurring mainly during the early stages of sleep at night. Its secretion is also increased during exercise, stress and fasting.
In old age, the level of growth hormone decreases; this explains in part the loss of muscle mass and muscle strength in later years, as well as thinning of the skin.
The effect of growth hormone is largely indirect: when growth hormone binds to target cells, they secrete the protein “insulin-like growth factor 1” (IGF-1) and it is this substance which directly causes most of the effects of growth hormone.

24. Thyroid-Stimulating Hormone
Thyroid-Stimulating Hormone
Produced by the anterior pituitary
Stimulates the normal development and secretory activity of the thyroid
Regulation of TSH release
⟶ Stimulated by thyrotropin-releasing hormone (TRH)
⟶ Inhibited by rising blood levels of thyroid hormones that act on the pituitary and hypothalamus
This hormone stimulates the thyroid gland to secrete thyroid hormones.
The secretion of TSH is subject to negative feedback by high blood levels of thyroid hormones; this stabilises blood levels of both TSH and thus of the thyroid hormones themselves. Conversely, high levels of TSH are elicited by low blood levels of thyroid hormones.

25. Adrenocorticotropic Hormone (ACTH)
Secreted by the anterior pituitary
Stimulates the adrenal cortex to release cortisol and aldosterone (to a lesser extent)
Regulation of ACTH release
⟶ triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythm
⟶ internal and external factors such as fever, hypoglycaemia, and stressors can alter the release of CRH

26. Gonadotropins
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secreted by the anterior pituitary
⟶ FSH stimulates gamete (egg or sperm) production
⟶ LH promotes production of gonadal hormones

27. Prolactin (PRL) Secreted by the anterior pituitary
Stimulates milk production
Regulation of PRL release
Primarily controlled by prolactin-inhibiting hormone (PIH) (dopamine)
Blood levels rise toward the end of pregnancy
Suckling stimulates PRH release and promotes continued milk production

28. Hypophysiotropic hormones
Physiological actions of
the pituitary

29. Pituitary & Hypothalamic Disorders
Hypothalamic-pituitary lesions present with a variety of signs, including pituitary hormone:
hypersecretion and hyposecretion,
sellar enlargement,
and visual loss

30. Pituitary & Hypothalamic Disorders
In adults, the most common cause of hypothalamic-pituitary dysfunction is a pituitary adenoma, of which the great majority are hypersecreting
Thus, the earliest symptoms of such tumors are due to endocrinologic abnormalities and include:
Early manifestation
Hypogonadism, the most frequent
diminished functional activity of the gonads
Late manifestation in patients with larger tumors or suprasellar extension
sellar enlargement
headache
and visual loss,

31. Gonadotrophins Disorders
Hyposecretion 
leads to amenorrhoea,
sterility
and loss of sexual potency.
In the young, the sex organs and secondary sexual characteristics fail to develop (delayed puberty)
Hypersecretion 
extremely rare,
in children it could lead to sexual precocity (excessive premature development)

32. Thyrotrophin Disorders
Hyposecretion 
produces a clinical picture similar to primary thyroid deficiency
Hypersecretion 
gives the symptoms of hyperthyroidism similar to Graves’ disease

33. Corticotrophin Disorders
Hyposecretion 
rare
causes failure of cortisol secretion,
a general lack of health and well being,
a reduced response to stress and skin depigmentation
Hypersecretion 
due to a pituitary microadenoma,
will result in Cushing’s syndrome

34. Prolactin Disorders Hyposecretion Hypersecretion
leads to failure of lactation in women
Hypersecretion 
may result from a pituitary tumour
principal symptoms are infertility and menstrual complaints
in men, decreased libido,
inadequate sperm production and impotence, whereas in women, there may be a complete lack of menstruation
inappropriate (non-pregnant) milk production
Dopamine, some drugs

35. GHRH Disorders Hyposecretion Hypersecretion
caused by hypothalamic or pituitary dysfunction
In childhood this leads to impairment of growth (dwarfism)
Hypersecretion
This usually results from a benign pituitary tumour
In young patients, this leads to gigantism
In adults, leads to acromegaly

36. Vasopressin Disorders
Hyposecretion 
caused by damage or dysfunction of the hypothalamus,
can lead to diabetes insipidus, 
excessively large amounts of dilute urine (10–15 liters/day) are produced by the kidneys
Hypersecretion 
rare condition of inappropriate AVP production is known as syndrome of inappropriate ADH (SIADH)

37. Hypopituitarism
Hypopituitarism is manifested by diminished or absent secretion of one or more pituitary hormones
Hypopituitarism is either:
a primary event
caused by destruction of the anterior pituitary gland
or a secondary phenomenon
resulting from deficiency of hypothalamic stimulatory factors normally acting on the pituitary

38. Assessment of Target Gland Function
If endocrine hypofunction is suspected, pituitary hormone deficiencies must be distinguished from primary failure of the thyroid, adrenals, or gonads
Baseline laboratory studies should include:
thyroid function tests (free T4)
and determination of serum testosterone levels
Testosterone is a sensitive indicator of hypopituitarism in women as well as in men

39. In primary target gland hypofunction, such as autoimmune polyglandular syndromes types 1 and 2 (APS 1 and 2), TSH, LH, FSH, or ACTH will be elevated
Low or normal values for these pituitary hormones suggest hypothalamic-pituitary dysfunction